METHOD OF USING REDUCED DIMENSIONALITY NMR SPECTROSCOPY FOR RAPID CHEMICAL SHIFT ASSIGNMENT AND STRUCTURE DETERMINATION OF PROTEINS

Abstract: The present invention discloses eight new redueced dimensionality (RD) triple resonance nuclear magnetic resonance (NMR) experiements for measuring chemical shift values of certain nuclei in a protein molecule. The RD 3D <u>HA</u>,<u>CA</u>,(CO),N,HN NMR experiment and the RD 3D <u>H</u>,<u>C</u>,(C-TOCSY-CO),N,HN NMR experiment are designed to yield "sequential" connectivities, while the RD 3D <u>H</u>< alpha beta >,<u>C</u>< alpha beta >,CO,HA NMR experiment and the RD 3D <u>H</u>< alpha beta >,<u>C</u>< alpha beta >,N,HN NMR experiment provide "intraresidue" connectivties. The RD 3D <u>H</u>,<u>C</u>,H-COSY NMR experiment, the RD 3D <u>H</u>,<u>C</u>,C, H-TOCSY NMR experiment, and the RD 2D <u>H</u>,<u>C</u>,H-COSY NMR experiment allow one to obtain assignments for aliphatic and aromatic side chain chemical shifts, while the RD 2D <u>HB</u>,<u>CB</u>;(CG,CD),HD NMR experiment provide information for the aromatic side chain chemical shifts. In addition, a method of conducting suites of RD triple resonance NMR experiments for high-throughput resonance assignment of proteins and identification of the location of secondary structure elements are disclosed.

Description: METHOD OF USING REDUCED DIMENSIONALITY NMR SPECTROSCOPY FOR RAPID CHEMICAL SHIFT ASSIGNMENT AND STRUCTURE DETERMINATION OF PROTEINS [0001] The present invention claims the benefit of U.S. Provisional Patent Application Serial No. 60/215,649, filed June 30, 2000, which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION [0002] The present invention relates to methods of using reduced dimensionality nuclear magnetic resonance (NMR) spectroscopy for obtaining chemical shift assignment and structure determination of proteins. BACKGROUND OF THE INVENTION [0003] The use of triple resonance (TR) nuclear magnetic resonance (NMR) experiments for the resonance assignment of polypeptide chains via heteronuclear scalar connectivities (Montelione et al., J. Am Chem. Soc, 111:5474-5475 (1989): Montelione et al.. J. Mam. Reson.. 87:183-188 (1989); Kay et al., J. Magn. Reson.. 89:496-514 (1990); Ikura et aL, Biochemistry. 29:4659-8979 (1990); Edison et al., Methods Enzvmol., 239:3-79 (1994)) is a standard approach which neatly complements the assignment protocol based on 1 H- 1 H nuclear Overhauser effects (NOE) (Wϋthrich, NMR of Proteins and Nucleic Acids, Wiley, New York (1986)). In addition, triple resonance NMR spectra are highly amenable to a fast automated analysis (Friedrichs et al., J. Biomol. NMR, 4:703-726 (1994); Zimmerman et al, J. Biomol. NMR. 4:241-256 (1994); Bartels et al., J. Biomol. NMR. 7:207-213 (1996); Morelle et al., J. Biomol. NMR. 5:154-160 (1995); Buchler et al., J. Maen. Reson.. 125:34-42 (1997); Lukin et al., J. Biomol. NMR. 9:151-166 (1997)), yielding the 13 ^ 0/β cnem i ca ι shi ts at an early stage of the assignment procedure. This enables both, the identification of regular secondary structure elements without reference to NOEs (Spera et al, J. Am. Chem. Soc. 113: 5490-5491 (1991)) and the derivation of (φ,ψ)-angle constraints which serve to reduce the number of cycles consisting of nuclear Overhauser enhancement spectroscopy (NOESY) peak assignment and structure calculation (Luginbϋhl et al., J. Magn. Reson.. B 109:229-233 (1995)). [0004] NMR assignments are prerequisite for NMR-based structural biology (Wtithrich, NMR of Proteins and Nucleic Acid. Wiley:New York (1986)) and, thus, for high-throughput (HTP) structure determination in structural genomics (Rost, Structure, 6:259-263 (1998); Montelione et al, Nature Struct. Biol., 6:11-12. (1999); Burley, Nature Struc Biol.. 7:932-934 (2000)) and for exploring structure-activity relationships (SAR) by NMR for drug discovery (Shuker et al., Science, 274:1531-1534 (1996)). The aims of structural genomics are to (i) explore the naturally occurring "protein fold space" and (ii) contribute to the characterization of function through the assignment of atomic resolution three- dimensional (3D) structures to proteins. It is now generally acknowledged that NMR will play an important role in structural genomics (Montelione et al., Nature Struc Biol.. 7:982-984 (2000)). The resulting demand for HTP structure determination requires fast and automated NMR data collection and analysis protocols (Moseley et al, Curr. Opin. Struct. Biol.. 9:635-642 (1999)). [0005] The establishment of a HTP NMR structural genomics pipeline requires two key objectives in data collection. Firstly, the measurement time should be minimized in order to (i) lower the cost per structure and (ii) relax the constraint that NMR samples need to be stable over a long period of measurement time. The recent introduction of commercial cryogenic probes (Styles et al., J. Magn. Reson.. 60:397-404 (1984); Flynn et al., J. Am Chem. Soc, 122:4823-4824 (2000)) promises to reduce measurement times by about a factor often or more, and will greatly impact the realization of this first objective. Secondly, reliable automated spectral analysis requires recording of a "redundant" set of multidimensional NMR experiments each affording good resolution (which requires appropriately long maximal evolution times in all indirect dimensions). Concomitantly, it is desirable to keep the total number of NMR spectra small in order to minimize "interspectral" variations of chemical shift measurements, which may impede automated spectral analysis. Straightforward consideration of this second objective would suggest increasing the dimensionality of the spectra, preferably by implementing a suite of four- or even higher-dimensional NMR experiments. Importantly, however, the joint realization of the first and second objectives is tightly limited by the rather large lower bounds of higher- dimensional TRNMR measurement times if appropriately long maximal evolution times are chosen. [0006] Hence, "sampling limited" and "sensitivity limited" data collection regimes are distinguished, depending on whether the sampling of the indirect dimensions or the sensitivity of the multidimensional NMR experiments "per se" determines the minimally achievable measurement time. As a matter of fact, the ever increasing performance of NMR spectrometers will soon lead to the situation where, for many protein samples, the sensitivity of the NMR spectrometers do not constitute the prime bottleneck determining minimal measurement times. Instead, the minimal measurement times encountered for recording conventional higher- dimensional NMR schemes will be "sampling limited," particularly as high sensitivity cryoprobes become generally available. As structure determinations of proteins rely on nearly complete assignment of chemical shifts, which are obtained using multidimensional 13 C, 15 N, 1H- TR NMR experiments (Montelione et al., J. Am Chem. Soc. 111 :5474-5475 (1989); Montelione, et al, J. Magn. Reson., 87:183-188 (1989); Ikura et al., Biochemistry, 29:4659-8979 (1990)), the development of TR NMR techniques that avoid the sampling limited regime represents a key challenge for future biomolecular NMR methods development. [0007] Reduced dimensionality (RD) TR NMR experiments (Szyperski et al., J. Biomol. NMR. 3:127-132 (1993); Szyperski et al., J. Am. Chem. Soc. 115:9307-9308 0993): Szyperski et al.. J. Magn. Reson.. B 105:188-191 (1994); Brutscher et al., J. Magn. Reson.. B 105:77-82 (1994); Szyperski et al., J. Magn. Reson.. B 108: 197-203 (1995); Brutscher et al., J. Biomol. NMR. 5:202-206 (1995); Lδhr et al., J. Biomol. NMR. 6:189-197 (1995); Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996); Szyperski et al., J. Magn. Reson.. 28:228-232 (1997); Bracken et al, J. Biomol. NMR. 9:94-100 (1997); Sklenar et al, J. Magn. Reson., 130:119-124 (1998); Szyperski et al, J. Biomol. NMR. 11:387-405 (1998)), designed for simultaneous frequency labeling of two spin types in a single indirect dimension, offer a viable strategy to circumvent recording NMR spectra in a sampling limited fashion. RD NMR is based on a projection technique for reducing the spectral dimensionality of TR experiments: the chemical shifts of the projected dimension give rise to a cosine-modulation of the transfer amplitude, yielding peak doublets encoding n chemical shifts in a n- dimensional spectrum (Szyperski et al., J. Biomol. NMR. 3:127-132 (1993); Szyperski et al., J. Am. Chem. Soc. 115:9307-9308 (1993)). As a key result, this allows recording projected four-dimensional (4D) NMR experiments with maximal evolution times typically achieved in the corresponding conventional 3D NMR experiments (Szyperski et al., J. Biomol. NMR. 3:127-132 (1993); Szyperski et al., J. Am. Chem. Soc. 115:9307-9308 (1993); Szyperski et al.,. I Magn. Reson. B 105:188-191 (1994); Szyperski et al, J. Magn. Reson.. B 108: 197-203 (1995); Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996); Szyperski et al., J. Magn. Reson.. 28:228-232 (1997); Bracken et al., J. Biomol. NMR. 9:94-100 (1997); Sklenar et al., J. Magn. Reson.. 130:119-124 (1998); Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998)). Furthermore, axial coherences, arising from either incomplete insensitive nuclei enhanced by polarization transfer (INEPT) or heteronuclear magnetization, can be observed as peaks located at the center of the doublets (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996)). This allows both the unambiguous assignment of multiple doublets with degenerate chemical shifts in the other dimensions and the identification of cross peak pairs by symmetrization of spectral strips about the position of the central peak (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996); Szyperski et al., J. Biomol. NMR. 11:387-405 (1998)). Hence, observation of central peaks not only restores the dispersion of the parent, higher- dimensional experiment, but also provides access to reservoir of axial peak magnetization (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996)). Historically, RD NMR experiments were first designed to simultaneously recruit both ! H and heteronuclear magnetization (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996)) for signal detection, a feature that has also gained interest for improving transverse relaxation-optimized spectroscopy (TROSY) pulse schemes (Pervushin et al., Proc. Natl. Acad. Sci. USA. 94:12366-12371 (1997); Salzmann et al., J. Am. Chem. Soc. 121:844-848 (1999); Pervushin et al, I Biomol. NMR, 12:345-348, (1998)). Moreover, RD two-spin coherence NMR spectroscopy (Szyperski et al., J. Biomol. NMR. 3:127-132 (1993)) subsequently also called zero-quantum double-quantum (ZQ/DQ) NMR spectroscopy (Rexroth et al, J. Am. Chem. Soc. 17:10389-10390 (1995)), served as a valuable radio- frequency (r.f.) pulse module for measurement of scalar coupling constants (Rexroth et al., J. Am. Chem. Soc. 17: 10389-10390 (1995)) and cross-correlated heteronuclear relaxation (Reif et al., Science, 276:1230-1233 (1997); Yang et al., J. Am. Chem. Soc. 121:3555-3556 (1999); Chiarparin et al., J. Am. Chem. Soc. 122:1758-1761 (2000); Brutscher et al.. J. Magn. Reson.. 130:346-351 (1998); Brutscher, Concepts Magn. Reson.. 122:207-229 (2000)). [0008] The present invention is directed to overcoming the deficiencies in the art. SUMMARY OF THE INVENTION [0009] The present invention relates to a method of conducting a reduced dimensionality three-dimensional (3D) HA,CA,(CO),N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having two consecutive amino acid residues, i-1 and i: (1) an α-proton of amino acid residue i-1, 1H α ; (2) an α- carbon of amino acid residue i-1, 13 C α / _ι; (3) a polypeptide backbone amide nitrogen of amino acid residue i, I5 N,-; and (4) a polypeptide backbone amide proton of amino acid residue i, 1H N ,-. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of ^M and 13 C ,--ι of amino acid residue i-1 are connected to the chemical shift evolutions of 15 N; and 1H N ,- of amino acid residue i, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α ,--ι and 15 N,- in a phase sensitive manner in two indirect time domain dimensions, tι( 13 C α ) and t 2 ( 15 N), respectively, and the chemical shift value of 1H N in a direct time domain dimension, t 3 (1H N ), and (2) to cosine modulate the 13 C α / .ι chemical shift evolution in t ! ( 13 C α ) with the chemical shift evolution of 1 H α , -1 . Then, the NMR signals are processed to generate a 3D NMR spectrum with a primary peak pair derived from the cosine modulating, where (1) the chemical shift values of 15 N,and 1H N ,- are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 ( 1 H N ), respectively, and (2) the chemical shift values of 1 H α , -1 and 13 C / .ι are measured in a frequency domain dimension, ω ! ( 13 C α ), by the frequency difference between the two peaks forming the primary peak pair and the frequency at the center of the two peaks, respectively. [0010] The present invention also relates to a method of conducting a reduced dimensionality three-dimensional (3D) H,C,(C-TOCSY-CO),N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift • values for the following nuclei of a protein molecule having two consecutive amino acid residues, i-1 and : (1) aliphatic protons of amino acid residue i-1, 1 H a , -ι; (2) aliphatic carbons of amino acid residue i-1, 13 C al ' ;-1 ; (3) a polypeptide backbone amide nitrogen of amino acid residue , 15 N,-; and (4) a polypeptide backbone amide proton of amino acid residue i, 1H N ,-. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 H a,1 ,-. 1 and l3 C dl i. \ of amino acid residue i-1 are connected to the chemical shift evolutions of I5 N,- and 1H N / of amino acid residue i, under conditions effective (1) to generate a NMR signal encoding the chemical shifts of 13 C all (-1 and 15 N,- in a phase sensitive manner in two indirect time domain dimensions, tι( 13 C ah ) and t 2 ( 15 N), respectively, and the chemical shift of 1H N ; in a direct time domain dimension, t 3 (1H N ), and (2) to cosine modulate the chemical shift evolutions of 13 C di in t ! ( 13 C a!i ) with the chemical shift evolutions of 1 H ali ;-1 . Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 15 N,and 1H N ,- are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 (1H N ), respectively, and (2) the chemical shift values of 1 H all , -1 and 13 C al . \ axe measured in a frequency domain dimension, ©i( 13 C al1 ), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0011] Another aspect of the present invention relates to a method of conducting a reduced dimensionality three-dimensional nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having an amino acid residue, : (1) a β-proton of amino acid residue i, 1H 15 ;; (2) a β-carbon of amino acid residue , 13 C β ,-; (3) an α-proton of amino acid residue i, 1 H α ,-; (4) an α -carbon of amino acid residue i, 13 C α ,; and (5) a polypeptide backbone carbonyl carbon of amino acid residue i, 3 C';. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 H α ,, 'H 13 ,-, 13 C α /, and 13 C β , are connected to the chemical shift evolution of I3 C',-, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α ; , 13 C β ,- and 13 C' ; - in a phase sensitive manner in two indirect time domain dimensions, ti( 13 C α/p ) and t ( 13 C), respectively, and the chemical shift value of 'H" in a direct time domain dimension, t 3 ( 1 H α ), and (2) to cosine modulate the chemical shift evolutions of 13 C ,- and 13 C P ,- in t ! ( 13 C α/p ) with the chemical shift evolutions of 1 H α ,- and W / , respectively. Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 13 C';and 1H α ,- are measured in two frequency domain dimensions, ω 2 ( 13 C) and ω 3 (1H α ), respectively, and (2) (i) the chemical shift values of 1H α ; and 1H β are measured in a frequency domain dimension, ω 1 ( 13 C /β ), by the frequency differences between the two peaks forming the peak pairs, and (ii) the chemical shift values of 13 C α ,-, and 13 C β ; are measured in a frequency domain dimension, ω^C"^), by the frequencies at the center of the two peaks forming the peak pairs. [0012] A further aspect of the present invention relates to a method of conducting a reduced dimensionality three-dimensional (3D) H^ β ,C α f3 ,N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having an amino acid residue, : (1) a β-proton of amino acid residue i, 1 H β ,; (2) a β-carbon of amino acid residue i, 13 C β ,-; (3) an α-proton of amino acid residue i, 'H",-; (4) an α-carbon of amino acid residue , 13 C α ,; (5) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N,-; and (6) a polypeptide backbone amide proton of amino acid residue i, l H ri i . The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 H α ,, 1H P ,-, 13 C α ,-, and 13 C P ,- are connected to the chemical shift evolutions of 15 N,- and 1 H N ,-, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α ,-, 13 C β ,- and 15 N,- in a phase sensitive manner in two indirect time domain dimensions, ^(^C 0 ^) and t 2 ( 15 N), respectively, and the chemical shift value of ! H ,- in a direct time domain dimension, t 3 (1H N ), and (2) to cosine modulate the chemical shift evolutions of 13 C α ; - and 13 C β ; in t^C^) with the chemical shift evolutions of 1 Η a i and 1H β , respectively. Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 15 N,- and 1H N ,- are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 (1H N ), respectively, and (2) (i) the chemical shift values of 1H α , and 1 H β ,- are measured in a frequency domain dimension, by the frequency differences between the two peaks forming the peak pairs, and (ii) the chemical shift values of 13 C α ,-, and 13 C β , are measured in a frequency domain dimension, ωι( 13 C α/ ' 5 ), by the frequencies at the center of the two peaks forming the peak pairs. [0013] The present invention also relates to a method of conducting a reduced dimensionality three-dimensional (3D) H,C,C,H-COSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1 H W , 13 C m , 1H", and 13 C" of a protein molecule where m and n indicate atom numbers of two CH, CH 2 or CH 3 groups that are linked by a single covalent carbon-carbon bond in an amino acid residue. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effects a nuclear spin polarization transfer where the chemical shift evolutions of 1H m and 13 C W are connected to the chemical shift evolutions of ] H" and 13 C", under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C m and 13 C" in a phase sensitive manner in two indirect time domain dimensions, ti( 13 C") and t 2 ( 13 C"), respectively, and the chemical shift value of 1H" in a direct time domain dimension, t 3 (1H"), and (2) to cosine modulate the chemical shift evolution of I3 C m in t 1 ( 13 C m ) with the chemical shift evolution of 1H m . Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 13 C" and 1H" are measured in two frequency domain dimensions, ω 2 ( 13 C") and ω 3 (1H"), respectively, and (2) the chemical shift values of 1H"' and 13 C * are measured in a frequency domain dimension, ωι( 13 C"), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0014] Another aspect of the present invention relates to a method of conducting a reduced dimensionality three-dimensional (3D) H,C,C,H-TOCS Y nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1H W , 13 C m , 1 H", and 13 C" of a protein molecule where m and n indicate atom numbers of two CH, CH 2 or CH 3 groups that may or may not be directly linked by a single covalent carbon-carbon bond in an amino acid residue. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1H m and 13 C are connected to the chemical shift evolutions of ] H" and 13 C, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C m and 13 C" in a phase sensitive manner in two indirect time domain dimensions, tι( I3 C m ) and t 2 ( 13 C"), and the chemical shift value of 1H" in a direct time domain dimension, t 3 (1H"), and (2) to cosine modulate the chemical shift evolution of 13 C in tι( 13 C m ) with the chemical shift evolution of l H m . Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 13 C" and 1H" are measured in two frequency domain dimensions, ω 2 ( 13 C") and ω 3 ( 1 H"), respectively, and (2) the chemical shift values of 1H m and 13 C are measured in a frequency domain dimension, ω 1 ( 13 C m ), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0015] A further aspect of the present invention relates to a method of conducting a reduced dimensionality two-dimensional (2D) HB,CB,(CG,CD),HD nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule: (1) a β-proton of an amino acid residue with an aromatic side chain, 1 H |3 ; (2) a β-carbon of an amino acid residue with an aromatic side chain, 13 C β ; and (3) a δ-proton of an amino acid • 1 £ residue with an aromatic side chain, H . The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 'H 13 and 13 C β are connected to the chemical shift evolution of 1H δ , under conditions effective (1) to generate NMR signals encoding the chemical shift value of 13 C β in a phase sensitive manner in an indirect time domain dimension, t ! ( 13 C β ), and the chemical shift value of ! H δ in a direct time domain dimension, t ( ! H δ ), and (2) to cosine modulate the chemical shift evolution of 13 C P in t 1 ( 13 C β ) with the chemical shift evolution of 1H 13 . Then, the NMR signals are processed to generate a 2D NMR spectrum with a peak pair derived from the cosine modulating where (1) the chemical shift value of ! H δ is measured in a frequency domain dimension, ω 2 ( ! H δ ), and (2) the chemical shift values of ! H β and 13 C β are measured in a frequency domain dimension, ωι( 13 C^), by the frequency difference between the two peaks forming the peak pair and the frequency at the center of the two peaks, respectively. [0016] The present invention also relates to a method of conducting a reduced dimensionality two-dimensional (2D) H,C,H-COSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1 H" ! , 13 C W , and H" of a protein molecule where m and n indicate atom numbers of two CH, CH 2 or CH 3 groups in an amino acid residue. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of l H m and 13 C * are connected to the chemical shift evolution of 1 H", under conditions effective (1) to generate NMR signals encoding the chemical shift value of I3 C m in a phase sensitive manner in an indirect time domain dimension, tι( 13 C m ), and the chemical shift value of 1H" in a direct time domain dimension, t 2 (1H"), and (2) to cosine modulate the chemical shift evolution of 13 C m in ( l3 ") with the chemical shift evolution of 1H m . Then, the NMR signals are processed to generate a 2D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift value of H" is measured in a frequency domain dimension, ω 2 (1H"), and (2) the chemical shift values of 1 H" ! and 13 C" are measured in a frequency domain dimension, ω 1 ( 13 C m ), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0017] Another aspect of the present invention relates to a method for sequentially assigning chemical shift values of an -proton, 1H α , an α-carbon, 13 C α , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD three-dimensional (3D) HA,CA,(CO),N,HN NMR experiment to measure and connect chemical shift values of the α-proton of amino acid residue i-1, 1H α ,--ι, the α-carbon of amino acid residue i-1, 13 C ,.ι, the polypeptide backbone amide nitrogen of amino acid residue i, 15 N,-, and the polypeptide backbone amide proton of amino acid residue i, 1H N ; and (2) a RD 3D HNNCAHA NMR experiment to measure and connect the chemical shift values of the α-proton of amino acid residue i, 1 H α ,-, the α-carbon of amino acid residue i, 13 C α ,-, 15 N,-, and ! H N . Then, sequential assignments of the chemical shift values of 1 H α , 13 C α , 15 N, and ] H N are obtained by (i) matching the chemical shift values of 1 H α , -1 and 13 C α ,-.ι with the chemical shift values of 1 H α ,- and 13 C α ; , (ii) using the chemical shift values of 1 H α / . i and 13 C α ,-_ι to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain. [0018] Yet another aspect of the present invention relates to a method for sequentially assigning chemical shift values of a β-proton, 1H β , a β-carbon, C , an α-proton, 1 H α , an α-carbon, 13 C α , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, ! H N , of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D H α/β C α β (CO)NHN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i-1, H' M , the β-carbon of amino acid residue i-1, 3 C β , -1 , the α-proton of amino acid residue i-1, 1H α / .ι, the α-carbon of amino acid residue i-1, 13 C α ;-1 , the polypeptide backbone amide nitrogen of amino acid residue i, 15 N ; , and the polypeptide backbone amide proton of amino acid residue i, 1H N ,- and (2) a RD 3D H^ β ,C |3 ,N,HN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 'H^,-, the β-carbon of amino acid residue i, 13 C β ,-, the α-proton of amino acid residue i, 1 H" , the α-carbon of amino acid residue i, 13 C α ,, 15 N,, and 1 JJ N i . Then, sequential assignments of the chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N are obtained by (i) matching the chemical shift values of the α- and β-protons of amino acid residue i-1, 1 H ot β ;-1 , and the α- and β-carbons of amino acid residue i-1, 13 C α/β 7-1 , with the chemical shift values of 'H 0 ^, and 13 C α β ,-, (ii) using the chemical shift values of 1 H α | Vι and i3 <χ/β _ ^ tQ identify he type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain. [0019] A further aspect of the present invention involves a method for sequentially assigning chemical shift values of aliphatic protons, I H a , aliphatic carbons, 13 C a , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of the aliphatic protons of amino acid residue i- 1, 1 H all ,. 1 , the aliphatic carbons of amino acid residue i-1, 13 C a ',_ ! , the polypeptide backbone amide nitrogen of amino acid residue i, 15 N fo and the polypeptide backbone amide proton of amino acid residue i, 1H N ,- and (2) a RD 3D H^ β ,C α β ,N,HN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1H β ;, the β-carbon of amino acid residue i, 13 C β ,-, the α-proton of amino acid residue i, 1 H α ,-, the α-carbon of amino acid residue i, 13 C α ,-, 15 N ; -, and 1H N ,-. Then, sequential assignments of the chemical shift values of 1H ali , 13 C ali , 15 N, and r H N are obtained by (i) matching the chemical shift values of the α- and β-protons of amino acid residue i-1, and the α- and β-carbons of amino acid residue i-1, 13 C α/β 7-1 , with the chemical shift values of 'H 0 ^,- and 13 C α β ,- of amino acid residue i, (ii) using the chemical shift values of 1 H aIl ;-1 and I3 C all , -1 to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain. [0020] The present invention also relates to a method for sequentially assigning chemical shift values of aliphatic protons, 1H al1 , aliphatic carbons, l C a , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of the aliphatic protons of amino acid residue i-1, 1 H al ',-ι, the aliphatic carbons of amino acid residue i-1 , 13 C ah , the polypeptide backbone amide nitrogen of amino acid residue i, 15 N,-, and the polypeptide backbone amide proton of amino acid residue i, 1H N ,- and (2) a RD 3D HNNCAHA NMR experiment to measure and connect the chemical shift values of the α-proton of amino acid residue i, 1 H α ,-, the α-carbon of amino acid residue i, 13 C α ,, 15 N,, and 1 H N ,-. Then, sequential assignments of the chemical shift values of 'H 3 ' 1 , 13 C ah , 15 N, and 1H N are obtained by (i) matching the chemical shift values of the α- proton of amino acid residue i-1, 1 H α ; -1 , and the α-carbon of amino acid residue i- 1, 13 C α ,-.ι, with the chemical shift values of 1H α ,- and I3 C α ,-, (ii) using the chemical shift values of 'H 3 ' 1 / - ! and 13 C ah /-1 to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain. [0021] Another aspect of the present invention involves a method for obtaining assignments of chemical shift values of 1H, 13 C and 15 N of a protein molecule. The method involves providing a protein sample and conducting four reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample, where (1) a first experiment is selected from the group consisting of a RD 3D H α/β C α/β (CO)NHN NMR experiment, a RD 3D HA,CA,(CO),N,HN NMR experiment, and a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment for obtaining sequential correlations of chemical shift values; (2) a second experiment is selected from the group consisting of a RD 3D HNNCAHA NMR experiment, a RD 3D H α β ,C α β ,N,HN NMR experiment, and a RD 3D HNN<CO,CA> NMR experiment for obtaining intraresidue correlations of chemical shift values; (3) a third experiment is a RD 3D H,C,C,H-COSY NMR experiment for obtaining assignments of sidechain chemical shift values; and (4) a fourth experiment is a RD 2D HB.CB.(CG.CD).HD NMR experiment for obtaining assignments of aromatic sidechain chemical shift values. [0022] The present invention discloses eight new RD TR NMR experiments and different combinations of those eight experiments as well as three other RD TR NMR experiments which allows one to obtain sequential backbone chemical shift assignments for determining the secondary structure of a protein molecule and nearly complete assignments of chemical shift values for a protein molecule including aliphatic and aromatic sidechain spin systems. [0023] RD NMR spectroscopy is a powerful approach to avoid recording TR NMR data for resonance assignment in the "sampling limited data acquisition regime." The set of NMR experiments for HTP structure determination as claimed in the present invention allows one to effectively adapt measurement times to sensitivity requirements. This is of outstanding value in view of HTP protein resonance assignment efforts in the forthcoming era of commercially available cryogenic probes. In particular, the rapid determination of a protein's secondary structure can greatly support fold prediction and thus protein target selection required for structural genomics (Montelione et al., Nature Struc Biol., 7:982-984 (2000), which is hereby incorporated by reference in its entirety). [0024] In addition, the present invention which discloses the sensitivity analysis of a suite of TRNMR experiments providing nearly complete assignments of chemical shift values of 1H, 13 C and 15 N of a protein molecule is unique and, thus, of general interest for the application of TRNMR schemes. The key insights obtained from this analysis are (i) that the sensitivity of the individual NMR experiments constituting the standard set derived here is comparable or better than the 3D HNNCACB NMR experiment, which has so far been routinely employed for proteins up to about 35 kDa, (Mer et al., J. Biomol. NMR, 17:179-180 (2000), which is hereby incorporated by reference in its entirety) and (ii) that data acquisition for most samples of proteins below 20 kDa will be in the undesired sampling limited regime when using conventional NMR schemes and cryogenic probes. (For 800 MHz systems, such probes today already offer a sensitivity of 6200:1 for a standard 0.1% ethylbenzene sample (Anderson, "High Q Normal Metal NMR Probe Coils," 42nd Experimental NMR Conference, Orlando, FL (2001), which is hereby incorporated by reference in its entirety).) Moreover, the sweep widths of all indirect dimensions of a multidimensional NMR experiment increase with increasing magnetic field strength (which implies increasing minimal measurement times). Hence, in view of this concomitant increase of sensitivity and sweep widths at highest magnetic fields and particularly considering the anticipated widespread use of cryogenic probes, a "change in paradigm" in biological NMR spectroscopy is expected with a new focus on research addressing the caveat of sampling limitation. This will foreseeably include development and application of data processing protocols that allow one to reduce the number of data points in the indirect dimensions without concomitantly sacrificing spectral resolution, i.e., linear prediction and maximum entropy methods (Stephenson, Prog. NMR Spectrosc. 20:515-626 (1988), which is hereby incorporated by reference in its entirety), approaches for non-linear sampling (Schmieder et al., J. Biomol. NMR. 4:483-490 (1994); Hoch, et al., NMR Data Processing. Wiley-Liss:New York, (1996), which are hereby incorporated by reference in their entirety), and the recently introduced filter diagonalization method (Wall et al., J. Chem. Phvs.. 102:8011-8022 (1995); Wall et al, Chem. Phvs. Lett.. 291:465-470 (1998); Hu et al, J. Magn. Reson.. 134: 76-87 (1998), which are hereby incorporated by reference in their entirety). [0025] Considering also random fractional deuteration of proteins for sensitivity enhancement, it is envisioned that the majority of protein structure determinations can possibly by accelerated by the application of RD NMR spectroscopy. In 2000, there were about eighty 750/800 MHz and three-hundred 600 MHz spectrometers in operation worldwide, which represent a commercial value of about $350 million (Cross, High Field NMR: a baseline study., National High Magnetic Field Laboratory, Tallahassee, Florida (2000), which is hereby incorporated by reference in its entirety). Assuming that about 50% of the instrument time is used for NMR structure determination, it is anticipated that the application of RD NMR technology promises to greatly impact on the optimized use of the large capital invested for NMR-based structural biology. BRIEF DESCRIPTION OF THE DRAWINGS [0026] Figures 1 A-K show the polarization transfer pathways (top) and stick diagrams of the peak pattern observed along ©}( C) (bottom) for the RD NMR experiments implemented for the present invention (the 3D H α β C α β (CO)NHN experiment, the 3D HACA(CO)NHN experiment, the 3D HC(C-TOCSY-CO)NHN experiment, the 3D HNNCAHA experiment, the 3D pj α/β £ α/β COHA experiment5 the 3D H p C α p NHN experiment, the 3D HNN<CO,CA> experiment, the 3D HCCH-COSY experiment, the 3D HCCH- TOCSY experiment, the 2D HBCB(CGCD)HD experiment, and the 2D 1H- TOC S Y-relay ed-HCH-CO S Y experiment, respectively). The boxes comprise nuclei whose chemical shifts are measured in the common dimension ω ls and the nuclei which are detected in quadrature in t ! are marked with an asterisk. Bold solid and hatched boxes indicate intraresidue and sequential connectivities, respectively, and the resulting signals sketched in the stick diagrams are represented accordingly. Those 13 C nuclei whose magnetization is used to detect central peaks (Szyperski et al, J. Am. Chem. Soc, 118:8146-8147 (1996), which is hereby incorporated by reference in its entirety), as well as the resulting subspectrum II shown at the bottom, are highlighted in grey. The magnetization is frequency labeled with single-quantum coherence of the encircled nuclei during t 2 and detected on the boxed protons. Except for Figure IG, the in-phase splittings 2ΔΩ(1H) are equal to 2κ ■ δΩ( 1 H)[γ( 1 H)/γ( 13 C)], where K, δΩ(1H) and γ(X) denote the scaling factor applied for 1H chemical shift evolution (set to 1.0 for the present study), the chemical shift difference with respect to the apparent 1H carrier position, and the gyromagnetic ratio of nucleus X, respectively. In Figure IG, the in-phase splittings 2ΔΩ( 13 C α ) are equal to 2κ • δΩ( 13 C α ), where K and δΩ( 13 C ) are the scaling factor applied for 13 C α chemical shift evolution 13 (set to 0.5 for the present study) and the chemical shift difference with respect to the apparent l C α carrier position, respectively. [0027] Figure 2A illustrates the experimental scheme for the 3D H α β C α β (CO)NHN experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for ! H chemical shift evolution during t ! is set to 1.0. The high-power 90° pulse lengths were: 5.9 μs for 1H, 15.4 μs for 13 C, and 38 μs for N. Pulses on C prior to t \ ( C) are applied at high power, and C decoupling during h( l Jϊ) is achieved using a (90 x -180 y -90 x ) composite pulse. Subsequently, the 90° and 180° pulse lengths applied for 13 C α β are adjusted to 47.5 μs and 42.5 μs, respectively, to minimize perturbation of 13 CO spins. The width of the 90° pulse applied on 13 CO pulse is 52 μs and the corresponding 180° pulses are applied with same power. A SEDUCE 180° pulse with a length of 200 μs is used to decouple 13 CO during t \ and τ . The length of the spin-lock purge pulses SL X and SL y are 1.2 ms and 0.6 ms, respectively. WALTZlόis employed to decouple 1H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers as well as to decouple 15 N during acquisition (r.f. = 1.78 kHz). The SEDUCE sequence is used for decoupling of 13 C during 15 N evolution period (r.f. = 1.0 kHz). The 1H r.f. carrier is placed at 0 ppm before the start of the semi constant time 1H chemical shift evolution period, and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. Initially, the 13 C and 15 N r. f. carriers are set to 43 ppm and 120.9 ppm, respectively. The C carrier is set to 56 ppm during the second τ 4 /2 delay. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (1 ms, 24 G/cm); G2 (100 μs, 16 G/cm); G3 (250 μs, 29.5 G/cm); G4 (250 μs, 30 G/ cm); G5 (1.5 ms, 20 G/cm);G6 (1.25 ms, 30 G/cm); G7 (500 μs, 8 G/cm); G8 (125 μs, 29.5 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: τ \ = 800 μs, τ = 3.1 ms, τ 3 = 3.6 ms, τ = 7.2 ms, τ 5 = 4.4 ms, τ 6 = 24.8 ms, τ 7 = 24.8 ms, τ 8 = 5.5 ms, τ = 4.6 ms, τjo = 1.0 ms. ^-frequency labeling is achieved in a semi constant-time fashion with ti 3 (0) = 1.7 ms, t ! b (0) = 1 μs, t (0) = 1.701 ms, Δt ! 3 = 33.3 μs, At = 19.3 μs, Δt]° = -14 μs. Hence, the fractional increase of the semi constant-time period with t \ equals to λ = 1 + Δtι° / Δt] 3 = 0.58. Phase cycling: φj = x; φ 2 = x,x,- x,-x; φ 3 = x, -x; φ = x, -x; φ 5 = x; φ6 = x, x, -x, -x; φ 7 = x; φ 8 (receiver) = x, -x, -x, x. The sensitivity enhancement scheme of Kay (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety) is employed, i.e., the sign of G 6 is inverted in concert with a 180° shift of φ . Quadrature detection in tι( 13 C) and t 2 ( 15 N) is accomplished by altering the phases φ 2 and φ 5 , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety). For acquisition of central peaks derived from 13 C steady state magnetization, a second data set with φi = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0028] Figure 2B illustrates the experimental scheme for the 3D HACA(CO)NHN experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for 1H chemical shift evolution during is set to 1.0. The high power 90° pulse lengths were: 5.8 μs for 1H and 15.4 μs for 13 C, and 38 μs for 15 N. Pulses on 13 C prior to ( i3 C) are applied at high power, and 13 C decoupling during tι( ! H) is achieved using a (90 x -180 y -90 x ) composite pulse. Subsequently, the 90° and 180° pulse lengths of 13 C α are adjusted to 51.5 μs and 46 μs, respectively, to minimize perturbation of the CO spins. The width of the 90° pulses applied to 13 CO pulse is 52 μs and the corresponding 180° pulses are applied with same power. A SEDUCE 180° pulse with a length 252 μs is used to decouple CO during t \ . The length of the spin-lock purge pulses SL X and SL y are 2.5 ms and 1 ms, respectively. WALTZ16 is employed to decouple 1H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers as well as to decouple 15 N during acquisition (r.f. = 1.78 kHz). The SEDUCE sequence is used for decoupling of 13 C α during the 15 N chemical shift evolution period (r.f. = 1.0 kHz). The 1H r.f. carrier is placed at 0 ppm before the start of the semi constant time 1H evolution period, and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. The 13 C α and 15 N r.f. carriers are set to 56.1 ppm and 120.9 ppm, respectively. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (1 ms, 24 G/cm); G2 (100 μs, 16 G/cm); G3 (1 ms, 24 G/cm); G4 (250 μs, 30 G/cm); G5 (1.5 ms, 20 G/cm); G6 (1.25 ms, 30 G/cm); G7 (500 μs, 8 G/cm); G8 (125 μs, 29.5 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: τi = 1.6 ms, τ 2 = 3.6 ms, τ 3 = 4.4 ms, τ 4 = τ 5 = 24.8 ms, τ 6 = 5.5 ms, τ = 4.6 ms, τ 8 = 1 ms. I H-frequency labeling is achieved in a semi constant-time fashion with t \ * (0) = 1.7 ms, t] b (0) = 1 μs, c (0) = 1.701 ms, Δti 3 = 60 μs, Δti b = 35.4 μs, Δt ! C = -24.6 μs. Hence, the fractional increase of the semi constant-time period with t \ equals to λ = 1 + Δtι° / Δtι a = 0.58. Phase cycling: φj = x; φ 2 = x, x, -x, -x; φ 3 = x, -x; φ 4 = x; φ 5 = x, x, -x, -x; φ 6 = x; φ?(receiver) = x, - x, -x, x. The sensitivity enhancement scheme of Kay (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety) is employed., i.e., the sign of G6 is inverted in concert with a 180° shift of φ . Quadrature detection in tι( I3 C) and t ( 15 N) is accomplished by altering the phases φ 2 and φ , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety). For acquisition of central peaks derived from 13 C steady state magnetization, a second data set with φ t = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0029] Figure 2C illustrates the experimental scheme for the 3D HC(C- TOCSY-CO)NHN experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for 1H chemical shift evolution during t] is set to 1.0. The high power 90° pulse lengths were: 5.8 μs for 1H and 15.5 μs for 13 C, and 38 μs for 15 N. Pulses on 13 C prior to tι( 13 C) are applied at high power, and C decoupling during tι( H) is achieved using a (90 x -180 y -90 x ) composite pulse. Subsequently, the 90° and 180° pulse lengths applied for I3 C are adjusted to 47.0 1 μs and 42.5 μs, respectively, to minimize perturbation of CO spins. The width of the 90° pulses applied to 13 CO pulse is 52 μs and the corresponding 180° pulses are applied with same power. A SEDUCE 180° pulse with a length 200 μs is used to decouple CO during t] and τ 4 period. WALTZ16 is employed to decouple H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers as well as to decouple 15 N during acquisition (r.f. = 1.78 kHz). The SEDUCE sequence is used for decoupling of 13 C α during the 15 N chemical shift evolution period (r.f. = 1.0 kHz). The ! H r.f. carrier is placed at 0 ppm before the start of the semi constant time 1H evolution period, and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. The 13 C and 15 N r. f. carriers are set to 43 ppm and 120.9 ppm, respectively. The lengths of the C spin-lock purge pulses, SL X , are 2.5 ms and 1.25 ms, respectively, before and after the carbon-carbon total 1 o correlation spectroscopy (TOCSY) relay. C isotropic mixing is accomplished using DIPSI-2 scheme with a r.f. field strength of 8.5 kHz. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (2 ms, 30 G/cm); G2 (100 μs, 8 G/ cm); G3 (200 μs, 4 G/cm); G4 (2 ms, 30 G/cm); G5(l .25 ms, 30 G/cm); G6 (500 μs, 5 G/ cm); G7 (125 μs, 29.5 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: % \ = 950 μs, τ 2 = 3.1 ms, τ 3 = 3.6 ms, τ 4 = 7.2 ms, τ = 4.45 ms, τ 6 = 24.8 ms, τ = 24.8 ms, τ 8 = 5.5 ms, τ = 4.8 ms, τio = 1 ms. 1H-frequency labeling is achieved in a semi constant-time fashion with a (0) = 1.7 ms, t ϊ b (0) = 1 μs, t ! C (0) = 1.701 ms, Δti 3 = 33.3 μs, Δti b = 19.3 μs, Δfι c = - 14 μs. Hence, the fractional increase of the semi constant-time period with t \ equals to λ = 1 + Δt] 0 / Δtι a = 0.58. Phase cycling: φi = x; φ 2 = x, -x; φ 3 = x, x, -x, -x; φ 4 = x, -x; φ 5 = x, x, -x, -x; φ 6 = x, x, -x, -x; φγ = x; Φs = 4x,4(-x); φ 9 = x; φ 10 (receiver) = x, -x, -x, x. The sensitivity enhancement scheme of Kay (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety) is employed, i.e., the sign of G5 is inverted in concert with a 180° shift of φ 9 . Quadrature detection in tι( 13 C) and t 2 ( 15 N) is accomplished by altering the phases φ 2 and φ , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety). For acquisition of central peaks derived from C steady state magnetization, a second data set with φ] = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0030] Figure 2D illustrates the experimental scheme for the 3D HNNCAHA experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for 1H chemical shift evolution during t! is set to 1.0. The 90° pulse lengths were: 5.8 μs for 1H and 21.6 μs for 13 C α , and 38 μs for 1S N, where the 90° pulse width for 13 C α is adjusted to generate a null of excitation in the center of the CO chemical shift range. The selective 90° ! H pulse used to flip back the water magnetization is applied for the 1.8 ms with the SEDUCE- 1 profile. WALTZ 16 is employed to decouple 1H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers as well as to decouple of 15 N (r.f. = 1.78 kHz) during acquisition. SEDUCE is used for decoupling of CO (max. r.f. = 3.0 kHz). WURST-2 is used for simultaneous band selective decoupling of 13 CO and 13 C β during x and the 1H and 13 C chemical shift evolution during t \ . 3.0 kHz sweeps at 176 ppm and 30 ppm, respectively, are used for decoupling of 13 CO and 13 C β (except for Ser, Thr, Ala). A sweep of 600 Hz is used at 14 ppm to decouple 13 C β of Ala. The 1H r.f. carrier is placed at the position of the solvent line at 4.78 ppm for the first three 1H pulses and the first WALTZ period, then switched to 0 ppm during the first delay τ /2, and subsequently switched back to the water line at 4.78 ppm during tι°. The 13 C α and 15 N carriers are set to 56.1 ppm and 120.9 ppm, respectively. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (500 μs, 8 G/cm); G2 (500 μs, 4 G/cm); G3 (1 ms, 30 G/cm); G4 (150 μs, 25 G/cm); G5 (1.25 ms, 30 G/cm); G6 (500 μs, 8G/cm); G7 (125 μs, 29.57 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays have the following values: τi = 4.6 ms, τ 2 = 5.5 ms, τ 3 = 24 ms, τ 4 = 2.0 1 " ms, τ 5 = 500 μs. C-frequency labeling is achieved in a semi constant-time fashion with h a (0) = 1.065 ms, t] b (0) = 49 μs, tj c (0) = 984 μs, Δt] 3 = 65 μs, Δt] b = 49 μs, Δt] C = -16 μs. Hence, the fractional increase of the semi constant-time period with t\ equals to λ = 1 + At\ c / Δt^ = 0.76. Note that the acquisition starts with the second complex point in t l5 while the first one is obtained by linear prediction. This ensures that a zero first-order phase correction is achieved along ©i. Phase cycling: φi = x, -x; φ 2 = x, x, -x, -x; φ 3 = x, -x, -x, x; φ =x, φ 5 = 4(x), 4(-x); φ 6 = x; φ (receiver) = x, -x, -x, x. The sensitivity enhancement scheme of Kay (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety) is employed, i.e., the sign of G5 is inverted in concert with a 180° shift of φ . Quadrature detection in tι( 13 C) and t 2 ( 15 N) is accomplished by altering the phases φ and φ 4 according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety). [0031] Figure 2E illustrates the experimental scheme for the 3D H α β C α/β COHA experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for the ! H chemical shift evolution during t] is set to 1.0. The high power 90° pulse lengths were: 5.9 μs for ! H, 15.4 μs for I3 C, and 38.2 μs for 15 N. The 90° and 180° pulse lengths of 13 C α/β were adjusted to 47.4 μs and 42.4 μs, respectively, to minimize perturbation of 13 CO spins. A 200 μs 180° pulse with SEDUCE profile is used to selectively invert 13 CO magnetization prior to the start oft]. The 90° and 180° pulses employed for excitation of 13 CO and subsequent magnetization transfer back to 13 C are of rectangular shape and 52 μs and 103 μs duration, respectively. The length of the spin-lock purge pulses SL X and SL y are 2.5 ms and 1 ms, respectively. WALTZ16 is employed to decouple ! H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers, and for decoupling of 15 N (r.f. = 1.78 kHz) during acquisition. GARP is used for decoupling of 13 C α (r.f. = 2.5 kHz). The ! H r.f. carrier is placed at the position of the solvent line at 0 ppm before the start of the first semi constant time 1H evolution period and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. Initially, the 13 C and 15 N r.f. carriers are set to 43 ppm and 120.9 ppm, respectively. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl = G2 (100 μs, 15 G/cm); G3 (2 ms, 25 G/cm); G4 (100 μs, 10 G/cm); G5 (1 ms, 27 G/cm); G6 (3 ms, 30 G/cm); G7 (1.3 ms, 20 G/cm); G8 (130 μs, 14 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: xj = 800 μs, t 2 = 2.8 ms, x 3 = 3.6 ms, τ 4 = 6.5 ms, τ 5 = 1.8 ms, τ = 1 ms, τ = 2.8 ms, τ 8 = 3.6 ms. 1H-frequency labeling is achieved in a semi constant-time fashion with t] 3 (0) = 1.1 ms, ti b (0) = 1 μs, t] c (0) = 1.701 ms, Δt] 3 = 33.3 μs, Δt] b = 19.3 μs, Δt] C = -14 μs. Hence, the fractional increase of the semi constant-time period with t \ equals to λ = 1 + Δt] C / Δti 3 = 0.58. Phase cycling: φ] = x; φ x = x, -x; φ 3 = x, -x, x, -x; φ 4 = x; φ 5 (receiver) = x, -x. Quadrature detection in t]( 13 C) and t 2 ( 15 N) is accomplished by altering the phases φ 2 and φ , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety). For acquisition of central peaks derived from C steady state magnetization, a second data set with φ] = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996), which is hereby incorporated by reference in its entirety). [0032] Figure 2F illustrates the experimental scheme for the 3D H p C α p NHN experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for the 1H chemical shift evolution during t \ is set to 1.0. The high power 90° pulse lengths were: 5.9 μs for 1H and 15.4 μs for 13 C, and 38 μs for N. Pulses on C prior to tj( C) are applied at high power, and C decoupling during tι(1H) is achieved using a (90 x -180 y -90 x ) composite pulse. Subsequently, the 90° and 180° pulse lengths of 13 C α β are adjusted to 49 μs and 43.8 μs to minimize perturbation of 13 CO spins. SEDUCE 180° pulses of 200μs pulse length are used to decouple CO. WALTZ16 is employed to decouple H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers, as well as to decouple 15 N (r.f. = 1.78 kHz). The 1H carrier is placed at the position of the solvent line at 0 ppm during the first semi constant time 1H evolution period, and then switched to the water line 4.78 ppm after the second 90° 1H pulse. The 13 C and 15 N r.f. carriers are set to 43 ppm and 120.9 ppm, respectively. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (1 ms, 24 G/cm); G2 (500 μs, 8 G/cm); G3 (250 μs, 15 G/cm); G4 (1 ms, 11 G/cm); G5 (500 μs, 20 G/cm); G6(500 μs, 4 G/cm); G7 (125 μs, 29.5 G/cm). All PFG pulses are of rectangular shape. The delays are: τ = 800 μs, τ 2 = 2.8 ms, τ 3 = 3.3 ms, τ 4 = 7.2 ms, τ 5 = 24 ms, τ 6 = 5.4 ms, τ = 4.8 ms, τ 8 = 1 ms. 1H-frequency labeling is achieved in a semi constant-time fashion with t] 3 (0) = 1.7 ms, tj b (0) = 1 μs, t] 0 (0) = 1.701 ms, Δt] a = 33.3 μs, Δt] b = 19.3 μs, Δt]° = -14 μs. Hence, the fractional increase of the semi constant-time period with t \ equals to λ = 1 + Δt] 0 / Δt] a = 0.58. Phase cycling: φ] = x; φ = x; φ 3 = x,-x; φ 4 = x, x, -x, -x; φ 5 = x; φ 6 (receiver) = x, -x. The sensitivity enhancement scheme of Kay (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety) is employed, i.e., the sign of G5 is inverted in concert with a 180° shift of φ 5 . Quadrature detection in t]( 13 C) and t ( 15 N) is accomplished by altering the phases φ 2 and φ 3 , respectively, according to States-TPPI. For acquisition of central peaks derived from 13 C steady state magnetization, a second data set with φj = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0033] Figure 2G illustrates the experimental scheme for the 3D HNN<CO,CA> experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for 13 C α chemical shift evolution during t 2 is set to 0.5. The high power 90° pulse lengths were: 5.8 μs for 1H and 38.5 μs for 15 N. The 90° and 180° pulse lengths of 13 C α were adjusted 54 μs and 48.8 μs to minimize perturbation of 13 CO spins. The length of the 90° pulses applied on 13 CO are 102 μs, and they possess the shape of a sine center lobe. The corresponding 180° pulses are applied with same power and shape. The selective 1H 90° pulse used for flip-back of water magnetization is applied for 1.8 ms with the SEDUCE-1 profile. WALTZ16 is employed to decouple 1H (r.f. field strength = 9.2 kHz) during the heteronuclear magnetization transfers as well as to decouple 15 N during acquisition (r.f. = 1.78 kHz). The SEDUCE sequence is used for decoupling of 13 C α during 15 N evolution period (r.f. = 0.9 kHz). The 13 C α and 15 N r.f. carriers are set to 176.5 ppm and 120.9 ppm, respectively. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (500 μs, 30 G/cm); G2 (500 μs, 5 G/cm); G3 (2 ms, 13 G/cm); G4 (750 μs, 20 G/cm); G5 (200 μs, 5 G/cm); G6 (100 μs, 12 G/cm); G7 (1.25 ms, 30 G/cm); G8 (300 μs, 5 G/cm); G9 (200 μs, 10 G/cm); G10 (125 μs, 29.5 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: xj = 4.6 ms, x 2 = 5.5 ms, x 3 = x 4 = 28 ms, x 5 = 1 ms. Phase cycling: φ] = x, x, -x, -x; φ 2 = x, -x; φ 3 = x; φ = x; φ 5 = 4(x), 4(- x); φ 6 = x; φ (receiver) = x, -x, -x, x. The sensitivity enhancement scheme of Kay (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety) is employed, i.e., the sign of G5 is inverted in concert with a 180° shift of φ 6 . Quadrature detection in tι( C) and t ( N) is accomplished by altering the phases φ and φ 4 , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incorporated by reference in its entirety). To shift the apparent 13 C α carrier position to 82.65 ppm, i.e., downfield to all 13 C α resonances, φ 3 is incremented in 60° steps according to TPPI. Note, that the acquisition was started with the ninth complex point and the first eight complex points along α>]( 13 CO) were obtained by linear prediction. This ensures that a zero first-order phase correction is achieved along <B] (Szyperski et al., J. Magn. Reson.. B 108: 197-203 (1995), which is hereby incorporated by reference in its entirety). [0034] Figure 2H illustrates the experimental scheme for the 3D HCCH- COSY experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for 1H chemical shift evolution during tj is set to 1.0. The high power 90° pulse lengths were: 5.8 μs for 1H and 15.4 μs for 13 C, and 38 μs for 15 N. The lengths of the ] H spin-lock purge pulses are: first SL X , 2.8 ms; second SL X , 1.7 ms; SL y : 4.9 ms. SEDUCE is used for decoupling of CO during t \ and t 2 (r.f. field strength = 1 kHz). WURSTis used for decoupling of 13 C during acquisition. The 1H carrier is placed at the position of the solvent line at 0 ppm before the start of the first semi constant time 1H evolution period, and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. The 13 C and 15 N r.f. carriers are set to 38 ppm and 120.9 ppm, respectively. The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (500 μs, 6 G/cm); G2 (500 μs, 7 G/cm); G3 (100 μs, 12 G/cm); G4 (100 μs, 12.5 G/cm); G5 (2 ms, 9 G/cm);G6 (500 μs, 5 G/cm); G7 (1.5 ms, 8 G/cm); G8 (400 μs, 6 G/cm). All gradients are applied along z-axis and are of rectangular shape. All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: X] = 1.6 ms, x 2 = 850 μs, x 3 = 2.65 ms, x = 3.5 ms, x 5 = 7 ms, x 6 = 1.6 ms, x = 3.2 ms. Phase cycling: φj = x; φ 2 = x, -x; φ 3 = x, -x; φ = x; φ 5 (receiver) = x, -x. Quadrature detection in t]( 13 C) and t 2 ( 13 C) is accomplished by altering the phases φ 2 and φ 3 , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety). For acquisition of central peaks derived from 13 C steady state magnetization, a second data set with φ] = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0035] Figure 21 illustrates the experimental scheme for the 3D HCCH- TOCS Y experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for 1H chemical shift evolution during t \ is set to 1.0. The high power 90° pulse lengths were: 5.8 μs for 1H and 15.4 μs for 13 C, and 38 μs for 15 N. C decoupling during t]( H) is achieved using a (90 x -180 y -90 x ) composite pulse. The lengths of the X H spin-lock purge pulses are: first SL X , 5.7 ms; second SL X , 0.9 ms; SL y , 4.3 ms. SEDUCE is used for decoupling of 13 CO during t \ and t (r.f. 1 field strength = 1 kHz), and GARP is employed for decoupling of C during acquisition (r.f. = 2.5 kHz). The 1H r.f. carrier is placed at the position of the solvent line at 0 ppm before the start of the first semi constant time ! H evolution period, and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. The 13 C α and 15 N r.f. carriers are set to 38 ppm and 120.9 ppm, respectively. The length of 13 C spin-lock purge pulses denoted SL X are of 2 ms duration. C isotropic mixing is accomplished using the DIPSI-2 scheme (r.f. = 8.5 kHz). The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (100 μs, 16 G/cm); G2 (2 ms, 15 G/cm); G3 (300 μs, 8 G/cm); G4 (500 μs, 30 G/cm); G5 (100 μs, 16 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: xj = 850 μs, x 2 = 3.2 ms. 1H-frequency labeling in t \ is achieved in a semi constant-time fashion with t] 3 (0) = 1.7 ms, t] b (0) = 1 μs, t] 0 (0) = 1.701 ms, Δt] a = 33.3 μs, Δtι b = 19.3 μs, Δt]° = -14 μs. 13 C-frequency labeling in t 2 is achieved in a semi constant-time fashion with t 2 3 (0) = 1120 μs, t 2 b (0) = 62.5 μs, t 2 c (0) = 995 μs, Δt 2 a = 160 μs, Δt 2 ° = 125 μs, Δt 2 c = -35 μs. These delays ensure that a 90° first-order phase correction is obtained along ω 2 ( 13 C). The fractional increases of the semi constant-time period in t \ equals to λ = 1 + Δt 2 c / Δt 2 a = 0.58, and in t 2 equals to λ = 1 + Δt 2 c / Δt 2 a = 0.78. Phase cycling: ψi = x; φ 2 = x, -x; Φ 3 = x; φ 4 = 2(x), 2(-x); φ 5 (receiver) = x,-x. Quadrature detection in t]( C) and t ( C) is accomplished by altering the phases φ 2 and φ 3 , respectively, according to States-TPPI (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety). For acquisition of central peaks derived from 13 C steady state magnetization, a second data set with φ] = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0036] Figure 2 J illustrates the experimental scheme for the 2D HBCB(CGCD)HD experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The scaling factor K for ! H chemical shift evolution during t \ is set to 1.0. The high power 90° pulse lengths were: 5.8 μs for 1H and 15.4 μs for 13 C. The first 180° pulse on 13 C prior to t]( 13 C) is applied at high power. Subsequently, the 90° pulse lengths of 13 C β is adjusted to 66 μs. The 180° 13 C β and ^C 3 " 5 pulses are of gaussian-3 shape and 375 μs duration. WALTZ 16 is used for decoupling of ! H (r.f. field strength = 4.5 kHz) during the magnetization transfer from 13 C α to "C™, and GARP is employed to decouple "C" 0 (r.f. = 2.5 kHz) during acquisition. The 1H r.f. carrier is placed at 0 ppm before the start of the semi constant time 1H evolution period, and then switched to the water line at 4.78 ppm after the second 90° 1H pulse. The 13 C r.f. carrier is set to 38 ppm during ωj( 13 C β ) and then switched to 131 ppm before the first 90° pulse on 13 C aro (pulse labeled with φ 4 ). The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (500 μs, 2 G/cm); G2 (1 ms, 22 G/cm); G3 (2 ms, 10 G/cm); G4 (1 ms, 5 G/cm); G5 (500 μs, 4 G/cm); G6 (1 ms, -14 G/cm); G7 (500 μs, -2G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: xi = 1.8 ms, x 2 = 8.8 ms, x 3 = 71 μs, x 4 = 5.4 ms, x 5 = 4.2 ms, x 6 = 710 μs, x = 2.5 ms. 1H- frequency labeling is achieved in a semi constant-time fashion with t] 3 (0) = 1.7 ms, t] b (0) = 1 μs, c (0) = 1.701 ms, Δt] a = 33.3 μs, Δtj b = 19.3 μs, Δt]° = -14 μs. Hence, the fractional increase of the semi constant-time period with t \ equals to λ = 1 + At \ I Δt] 3 = 0.58. Phase cycling: φ] = x; φ 2 = x; φ 3 = x, y, -x, -y; φ = 4(x), 4(-x); φ 5 (receiver) = x, -x, x, -x, -x, x, -x, x. Quadrature detection in t]( 13 C) is accomplished by altering the phases φ 2 respectively, according to States-TPPI. For acquisition of central peaks derived from 13 C steady state magnetization, a second data set with φi = -x is collected. The sum and the difference of the two resulting data sets generate subspectra II and I, respectively, containing the central peaks and peak pairs. [0037] Figure 2K illustrates the experimental scheme for the 2D ! H- TOCSY-relayed-HCH-COSY experiment. Rectangular 90° and 180° pulses are indicated by thin and thick vertical bars, respectively, and phases are indicated above the pulses. Where no radio-frequency (r.f.) phase is marked, the pulse is applied along x. The high-power 90° pulse lengths were: 5.9 μs for ! H and 15.4 μs for 13 C. The 1H r.f. carrier is placed at the position of the solvent line at 4.78 ppm, and the 13 C carrier is set to 131 ppm. GARP is used for 13 C decoupling during acquisition (r.f. field strength = 2.5 kHz), and 1H isotropic mixing is accomplished using the DIPSI-2 scheme (r.f. = 16 kHz). The duration and strengths of the pulsed z-field gradients (PFGs) are: Gl (1 ms, -10 G/cm); G2 (500 μs, 6 G/cm); G3 (500 μs, 7.5 G/cm); G4 (1 ms, 22 G/cm). All PFG pulses are of rectangular shape. A recovery delay of at least 100 μs duration is inserted between a PFG pulse and an r.f. pulse. The delays are: X] = 3.0 ms, x 2 = 15.38 ms. Phase cycling: φ] = x, -x; φ 2 = x, x, y, y, -x, -x, -y, -y; φ 3 = 4(x),4(y), 4(-x), 4(-y); φ 4 = x, x, -x, -x; φs(receiver) = x, -x, x, -x, -x, x, -x, x. Quadrature detection in ^ι( 13 C) is accomplished by altering the phase φj according to States-TPPI. [0038] Figure 3 illustrates the polypeptide chemical shifts correlated by the various spectra constituting the "standard set" of TRNMR experiments identified for efficient HTP resonance assignment of proteins. The nuclei for which the chemical shifts are obtained from a given experiment are boxed and labeled accordingly. [0039] Figures 4A-F illustrate the sequential connectivities in RD NMR spectra. Figures 4A-C show the cross sections along ωj( 13 C) taken from the subspectra I, which exhibit peak pairs arising from H chemical shift evolution, of 3D HACA(CO)NHN (Figure 4A), 3D H α/β C α β (CO)NHN (Figure 4B) and 3D HC(C-TOCSY-CO)NHN (Figure 4C) (21 ms mixing time). The in-phase splittings encoding the 1 H α (Figure 4A), 1H β (Figure 4B) and 1H V (Figure 4C) chemical shifts of Gin 26 are indicated. Figures 4D-F show the corresponding cross sections taken from subspectra II, which exhibit central peaks. The signals arising from 13 C α (Figure 4A), 13 C β (Figure 4B) and 13 C γ (Figure 4C) of Gin 26 are indicated. Chemical shifts are given relative to 2,2-dimethyl-2-silapentane-5- sulfonate (DSS). [0040] Figure 5 illustrates the sensitivity of TR NMR experiments relative to peak pair detection in 3D HACA(CO)NHN (left-most bar). As indicated on the top of the figure, the experiments are grouped according to providing interresidue ("inter"), intraresidue ("intra"), aliphatic side chain ("ali") and aromatic side chain ("aro") connectivities. For RD NMR experiments, the sensitivity of peak pair (black bars) and central peak (grey bars) detection was analyzed separately. The yield of peak detection (in percent) is indicated on the top of the bars. Note that only those peak categories encoding the prime information to be obtained from a given spectrum, i.e., irøtrøresidual connectivities in HNNCAHA (Figure ID), H^C^COHA (Figure IE), H^C α p NHN (Figure IF) and HNNCACB, correlation peaks in HCCH-COSY and relay connectivities in HCCH TOCSY, and only peaks exhibiting a S/N ratio larger than 3 were considered for this plot. For well-resolved RD peak pairs the averaged S/N ratio of the two individual peaks is given. In cases where only one of the two peaks is well resolved, only the value for the resolved peak was considered. As an example, the insert shows the S/N distributions obtained for the intraresidue peak pairs detected in 3D HNNCAHA. Black and grey bars correspond to spectra acquired with and without adiabatic 13 C β -decoupling, respectively (Abragam, Principles of Nuclear Magnetism, Clarendon Press:Oxford (1986); Ernst et al., Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press: Oxford (1987), which are hereby incoφorated by reference in their entirety). [0041] Figures 6A-C illustrate the intraresidue connections in RD NMR spectra: cross sections along α>]( 13 C) taken from 3D HNNCAHA (Figure 6A), subspectrum I of 3D H^C^COHA (Figure 6B) and subspectrum I of 3D H a p C α p NHN (Figure 6C). The in-phase splittings encoding the 1H α of Glu 24 and Asn 23 (Figure 6A) and 1H β of Glu 24 (Figure 6B) are indicated. Chemical shifts are given relative to DSS. [0042] Figure 7 is the schematic presentation of the RD NMR-based HTP resonance assignment strategy using the "standard set" of experiments identified in the framework of the present study. The central role of 3D H α β C α/β (CO)NHN is shown for creating sequential connectivities via (ϊ) 13 C α and 1 H α shift measurements (HNNCAHA; Figure 8), via (ii) 13 C α and 13 C β shift measurements (HNNCACB), and via (iii) 13 C=O shift measurements (H α β C α/β COHA/ HNNCAHA and HNN<CO,CA>; Figure 9). This key role is further evidenced when employing 3D H β C α β (CO)NHN also for assigning aliphatic (HCCH- COS Y/TOCS Y; Figures 9 and 10) and aromatic side chains (HBCB(CGCD)HD and 1H-TOCSY-relayed HCH-COSY: Figure 12). Black double-headed arrows indicate connectivities which are established based on matching of peak patterns along α>]( 13 C) of the spectra, and grey arrows indicate that the combined use of the two spectra connected by the arrow requires the conversion of in-phase splittings into chemical shifts. Each box shows the peak patterns expected along CD], and the chemical shifts that are measured in the other dimensions are given above the corresponding boxes. Two cross sections are sketched for RD NMR experiments which yield two subspectra labeled with I and II, which comprise peak pairs and central peaks, respectively. [0043] Figure 8 shows the sequential resonance assignment from 3D H α β C α/β (CO)NHN / 3D HNNCAHA. Contour plot of [cO]( 13 C), ω 3 (1H N )]-strips taken from subspectrum I (strips labeled with Al) and subspectrum II (strips labeled with All) of 3D H α/β C tχ/β (CO)NHN, and from 3D HNNCAHA (strips labeled with B) are shown. The strips were taken at the 5 N chemical shifts (indicated at the top) of residues 51 to 55 and are centered about their 1H N chemical shift. The sequence-specific resonance assignments of the amide chemical shifts are given at the top of each strip and are referred to as i. Ω(1H α/β ;-1 ) and Ω( 13 C α β M ) obtained from 3D H α β C α β (CO)NHN are given in the strips Al and All of residue i. Corresponding peak pairs in Al and central peaks in All are connected by dashed lines, and sequential connectivities are indicated by solid lines for both peak pairs and central peaks. Dashed and solid contour lines represent negative and positive peaks, respectively, and sequential connectivities established via the central peaks and via the peak pairs are indicated by solid and dotted lines, respectively. Note, that the near-degeneracy of 13 C α chemical shifts in the polypeptide segment Asn 52-Asp 53-Ala 54 is neatly resolved by the measurement of 1 H tx chemical shifts encoded in the in-phase splittings of the peak pairs. Chemical shifts are relative to DSS. [0044] Figures 9A-B show the sequential resonance assignment based on 3D H α β C α β (CO)NHN / 3D H^C^COHA combined with 3D HNN<CA,CO> (Figure 7). The amino acid residue on which the NMR signal was detected is indicated at the bottom of the strips. Figure 9A shows the matching of ω 1 ( 13 C ct/β ) peak patterns in 3D H^C^COHA (strips labeled with "a") and 3D H α β C α/β (CO)NHN ("b") yields putative intraresidue 1H α/β / 13 C α β - 13 C=O correlations: on the strips taken from 3D H α/β C α/β COHA the 13 C=O chemical shift is indicated. 3D HNN<CA,CO> yields the sequential 13 C=O- 13 C α correlations (Figure 9B): the carbonyl chemical shifts have to match those shown in Figure 9A, and are indicated on the left of the figure. Proton and carbon chemical shifts are given in ppm and are relative to DSS. [0045] Figures 10A-C shows the assignment of aliphatic spin systems using 3D H α/β C α β (CO)NHN / 3D HCCH-COSY exemplified for Lys 4. Cross sections taken along CD]( 13 C) from 3D H α β C α/β (CO)NHN (Figure 10A) and subspectrum I of 3D HCCH-COSY (Figure 10B) are shown. The signals in 3D H α β C α β (CO)NHN were detected on the backbone amid proton of the succeeding residue Phe 5 (the 15 N and 1H N chemical shifts are indicated on the right). The cross sections taken from HCCH-COSY exhibit signals which were detected on 1H α , 1H β , 1H γ and 1H δ of Lys 4, respectively (from the bottom to the top). The in- phase splittings encode the 1H β , 1H Y , 1H δ and 1H ε chemical shifts and serve to obtain the desired correlations as indicated by dashed vertical lines. Note that the n ι peak signs vary because of aliasing along ω ( C). In Figure IOC, a CD]( C) cross section from 3D HCCH-TOCSY is shown. The signal was detected on l JJ of Lys 4, and the crucial α CH- γ CH relay connectivity is indicated (see also Figure 9). Proton and carbon chemical shifts are relative to DSS. [0046] Figures 11 A-C show the assignment of aliphatic side chains exemplified for Lys 4 (see also Figure 12). Pairs of cross sections taken from 3D HCCH-COSY and TOCSY are shown. These exhibit signals detected on 1 H α (Figure 11 A), 1H β (Figure 1 IB) and 1H γ (Figure 11C) of Lys 4, respectively. The crucial α CH- γ CH relay connectivities, which resolve potential overlap in HCCH- COSY, are indicated with vertical lines. Note that the peak signs vary because of aliasing along ω 2 ( 13 C). The assignment of the peak pairs is shown in Figure 10. [0047] Figures 12 A-C show the assignment of aromatic side chains exemplified for His(-4) and His 18, and Tyr 14. A composite plot of [ω 1 ( 13 C),ω 3 ( 1 H N )]-strips taken from 3D H α β C α β (CO)NHN comprising the cθ]( 13 C) peaks of all aromatic side chains in the polypeptide segment (-5)-58 of Z-domain, the 2D HBCB(CGCD)HD spectrum (Figure 12B) as well as a spectral region taken from 2D 1H-TOCSY-relayed HCH-COSY (Figure 12C) are shown. The entire 2D 1H-TOCSY-relayed HCH-COSY spectrum, which also contains cross peaks arising from ε CH of the histidinyl residues, is shown in the upper right of the figure. Correlations belonging to His(-4), His 18, and Tyr 14 are connected with long-dashed, dashed and grey solid lines, respectively. In Figure 12C, peaks arising from α CH moieties (which are not required for connecting the aromatic spin systems) are labeled with an asterisk. DETAILED DESCRIPTION OF THE INVENTION [0048] The present invention discloses eight new RD TR NMR experiments and different combinations of those eight experiments as well as three other RD TR NMR experiments which allows one to obtain sequential backbone chemical shift assignments for determining the secondary structure of a protein molecule and nearly complete assignments of chemical shift values for a protein molecule including aliphatic and aromatic sidechain spin systems. Figure 1 provides a survey of (i) the names, (ii) the magnetization transfer pathways and (iii) the peak patterns observed in the projected dimension of specific embodiments of the 8 new RD NMR experiments disclosed by the present invention as well as 3 other RD NMR experiments that have previously been published. The group comprising the first three experiments are designed to yield "sequential" connectivities via one-bond scalar couplings: 3D H α/β C α β (CO)NHN (Figure 1A; Szyperski et al., J. Magn. Reson., B 105: 188-191 (1994), which is hereby incoφorated by reference in its entirety), 3D HACA(CO)NHN (Figure IB), and 3D HC(C-TOCSY-CO)NHN (Figure 1C). The following three experiments provide "intraresidual" connectivities via one-bond scalar couplings: 3D HNNCAHA (Figure ID; Szyperski et al., J. Biomol. NMR. 11:387-405 (1998), which is hereby incoφorated by reference in its entirety), 3D H^C^COHA (Figure IE), and 3D H α β C α/β NHN (Figure IF). 3D HNN<CO,CA> (Figure IG; Szyperski et al., J. Magn. Reson.. B 108: 197-203 (1995); Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996), which are hereby incoφorated by reference in their entirety) offers both intraresidual ! H N - I3 C α and sequential 1H N - 13 C connectivities. Although 3D HNNCAHA (Figure ID), 3D H^£ α p NHN (Figure IF) and 3D HNN<CO,CA> (Figure 1 G) also provide sequential connectivities via two-bond I3 C α / .]- I5 N scalar couplings, those are usually smaller than the one-bond couplings (Cavanagh et al., Protem NMR Spectroscopy, Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety), and obtaining complete backbone resonance assignments critically depends on experiments designed to provide sequential connectivities via one-bond couplings (Figures 1D-F). 3D HCCH- COSY (Figure 1H) and 3D HCCH-TOCSY (Figure II) allow one to obtain assignments for the "aliphatic" side chain spin systems, while 2D HBCB(CDCG)HD (Figure 1J) and 2D 1H-TOCSY-relayed HCH-COSY (Figure IK) provide the corresponding information for the "aromatic" spin systems. [0049] The RD NMR experiments are grouped accordingly in Table 1, which lists for each experiment (i) the nuclei for which the chemical shifts are measured, (ii) if and how the central peaks are acquired and (iii) additional notable technical features. State-of-the art implementations (Cavanagh et al., Protein NMR Spectroscopy, Academic Press, San Diego, (1996); Kay, J. Am. Chem. Soc. 115:2055-2057 (1993); Grzesiek et al., J. Magn. Reson.. 99:201-207 (1992); Montelione et al., J. Am. Chem. Soc. 114:10974-10975 (1992); Boucher et al, J. Biomol. NMR. 2:631-637 (1992); Yamazaki et al., J. Am. Chem. Soc. 115:11054-11055 (1993); Zerbe et al, J. Biomol. NMR. 7:99-106 (1996); Grzesiek et al., J. Biomol. NMR. 3:185-204 (1993), which are hereby incoφorated by reference in their entirety) making use of pulsed field z-gradients for coherence selection and/or rejection, and sensitivity enhancement (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety) were chosen, which allow executing these experiments with a single transient per acquired free induction decay (FID). Semi (Grzesiek et al., J. Biomol. NMR. 3:185-204 (1993), which is hereby incoφorated by reference in its entirety) constant-time (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety) chemical shift frequency-labeling modules were used throughout in the indirect dimensions in order to minimize losses arising from transverse nuclear spin relaxation. Figures 2A-2K provide comprehensive descriptions of the RD NMR r.f. pulse sequences used in the 11 RD NMR experiments including eight previously unpublished RD NMR r.f. pulse schemes. Table 1. Reduced Dimensionality NMR Experiments for HTP Resonance Assignment Experiment Nuclei for which the chemical shifts are Acquisition of (see Figure 1) correlated 3 ' 1 ' central peaks c 3D spectra for sequential backbone connectivities: (A) H α/β C α/β (CO)NHN 'H^,,, ,3 C β M , 'H",,,, 13 C α M , ,s N h. , H N , (B) HACA(CO)NHN 'H a M , I3 C α M , ,5 N„ Η N ,. (C) HC(C-TOCSY- CO)NHN Η"",-.,, "C 3 ",.,, 15 N,-, Η N ,- 3D spectra for intraresidual backbone connectivities: (D) HNNCAHA ι b",d •H",, 13 C α „ 15 N,, 'H N , INEPT (E) H^C^COHA 'H β ,, ,3 C β ; , 'H", ,3 C α ,, ,3 C=0; 13 c (F) H α/β C α β NH Η β ,, 13 C β ( , l U a „ 13 C α ; , 15 N,, 'H N , ,3 C 3D spectrum for intra- and sequential backbone connectivities: (G) HNN<CO,CA> b "CO,,,, ,3 C α ,, 5 N,, INEPT 3D spectra for assignment of aliphatic resonances^ (H) HCCH-COSY 'H m , l3 C m , 1 H m 13 C„ (I) HCCH-TOCSY Ή ITT 13 r lττ I3 13 C 2D spectra for assignment of aromatic resonances: 6 (J) HBCB(CGCD)HD Η β , 13 C β , ] H δ (K) Η-TOCSY-HCH-COSY Η m , I3 C m , Η m none a i-1, i: numbers of two sequentially located amino acid residues. b Sequential connectivities via two-bond 13 C α ,.ι- 15 N / scalar couplings are not considered in this table. c approach-1 (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996), which is hereby incoφorated by reference in its entirety): use of incomplete INEPT (rows labeled with "INEPT"); approach-2 (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996), which is hereby incoφorated by reference in its entirety): use of 13 C steady state magnetization (rows labeled with " 13 C"). d adiabatic I3 C β -decoupling (Kupce et al., J. Magn. Reson.. A 115:273-277 (1995); Matsuo et al., J. Magn. Reson. B 113 : 190- 194 ( 1996), which are hereby incoφorated by reference in their entirety) is employed during delays with transverse 13 C α magnetization. e m, n, p: atom numbers in neighboring CH, CH 2 or CH 3 groups. f acquisition of central peaks is prevented by the use of spin-lock purge pulses (flanking the total correlation relay) to obtain pure phases. The 3D HA,CA,(CO),N,HN experiment [0050] The present invention relates to a method of conducting a reduced dimensionality (RD) three-dimensional (3D) HA,CA,(CO),N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having two consecutive amino acid residues, i-1 and i: (1) an α-proton of amino acid residue i-1, 1H ,--ι; (2) an α- carbon of amino acid residue i-1, 13 C α ,-.j; (3) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N,; and (4) a polypeptide backbone amide proton of amino acid residue i, 1H ;. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 H α ; -1 and 13 C ;-1 of amino acid residue i-1 are connected to the chemical shift evolutions of 15 N,- and 1H N ,- of amino acid residue i, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C™ .i and 15 N; in a phase sensitive manner in two indirect time domain dimensions, t 1 ( 13 C tx ) and t 2 ( 15 N), respectively, and the chemical shift value of 1H N ,- in a direct time domain dimension, t 3 ( ! H N ), and (2) to cosine modulate the 13 C α , -1 chemical shift evolution in t]( 13 C α ) with the chemical shift evolution of 1H α ,-]. Then, the NMR signals are processed to generate a 3D NMR spectrum with a primary peak pair derived from the cosine modulating, where (1) the chemical shift values of 15 N,- and 1H N , are measured in two frequency domain dimensions, ω ( 15 N) and ω 3 ( 1 H N ), respectively, and (2) the chemical shift values of 'H" .] and 13 C α ;-1 are measured in a frequency domain dimension, α>]( 13 C ), by the frequency difference between the two peaks forming the primary peak pair and the frequency at the center of the two peaks, respectively. [0051] In addition, the method of conducting a RD 3D HA,CA,(CO),N,HN NMR experiment can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C ,-.] and I5 N; in a phase sensitive manner in t]( 13 C α ) and t 2 ( 15 N) and the chemical shift value of 1H N ,- in t 3 (1H N ), and (2) to avoid cosine modulating the 13 C α , -1 chemical shift evolution in tι( 13 C α ) with the chemical shift evolution of 1 H α , -1 for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with an additional peak located centrally between two peaks forming the primary peak pair which measures the chemical shift value of 13 C α ,.] along <B]( 13 C a ). That additional peak can be derived from 13 C α nuclear spin polarization. One specific embodiment (3D HACA(CO)NHN) of this method is illustrated in Figure IB, where the applying radiofrequency pulses effects a nuclear spin polarization transfer where a radiofrequency pulse is used to create transverse 'H" .] magnetization, which is transferred to 13 C α ;-1 , to 15 N,-, and to 1H N ,-, to generate the NMR signal. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2B to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2B, where phase φ] of the first 1H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the primary peak pair and a second NMR subspectrum derived from the adding which contains the additional peak located centrally between the two peaks forming the primary peak pair. [0052] In addition, the method of conducting a RD 3D HA,CA,(CO),N,HN NMR experiment can involve applying radiofrequency pulses under conditions effective to additionally cosine modulate the 13 C α ;.] chemical shift evolution in t]( 13 C α ) with the chemical shift evolution of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C',_]. Then, the NMR signals are processed to generate a 3D NMR spectrum with two secondary peak pairs where (1) each of the secondary peak pairs is derived from a different one of the peaks of the primary peak pair, and (2) the chemical shift value of 13 C' (-1 is measured along a>]( 13 C a ) by the frequency difference between the two peaks forming one of the secondary peak pairs. This method can further involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α r-1 and 15 N,- in a phase sensitive manner in t ! ( 13 C α ) and t 2 ( 15 N) and the chemical shift value of 1H N ; in t 3 (1H N ), (2) to cosine modulate the 13 C°V] chemical shift evolution in t]( 13 C α ) with the chemical shift evolution of C' ;-1 , and (3) to avoid cosine modulating the 13 C .] chemical shift evolution in tι( 13 C α ) with the chemical shift evolution of 1 H α ; -1 . Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with an additional secondary peak pair located between the two secondary peak pairs which measures the chemical shift values of 13 C' / -ι and 13 C α ;-1 along ω ! ( 13 C ), by the frequency difference between the two peaks forming the additional secondary peak pair and the frequency at the center of the two peaks, respectively. That additional secondary peak pair can be derived from I3 C α nuclear spin polarization. One specific embodiment (3D HACA(CO)NHN) of this method is illustrated in Figure IB, where the applying radiofrequency pulses effects a nuclear spin polarization transfer where a radiofrequency pulse is used to create transverse 1 H α !-1 magnetization, which is transferred to 13 C α ,-.ι, to 15 N;, and to 1 H N ; , to generate the NMR signal. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2B to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2B, where phase φi of the first ! H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the two secondary peak pairs and a second NMR subspectrum derived from the adding which contains the additional peak located centrally between the primary peak pair. [0053] In an alternate embodiment, the RD 3D HA,CA,(CO),N,HN NMR experiment can be modified to a RD 2D HA,CA,(CO,N),HN NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of 15 N, does not occur. Then, the NMR signals are processed to generate a two dimensional (2D) NMR spectrum with a peak pair where (1) the chemical shift value of 1 H N ,- is measured in a frequency domain dimension, ω 2 (1H N ), and (2) the chemical shift values of 'H".] and 13 C α ,.] are measured in a frequency domain dimension, ω]( 13 C α ), by the frequency difference between the two peaks forming the primary peak pair and the frequency at the center of the two peaks, respectively. [0054] In an alternate embodiment, the RD 3D HA,CA,(CO),N,HN NMR experiment can be modified to a RD 4D HA,CA,CO,N,HN NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 CVι, occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C'M in a phase sensitive manner in an indirect time domain dimension, t 4 ( 13 C). Then, the NMR signals are processed to generate a four dimensional (4D) NMR spectrum with a peak pair where (1) the chemical shift values of 15 N,, 1 H N ,- and 13 C' ;-/ are measured in three frequency domain dimensions, ω 2 ( 15 N), ω 3 (1H N ), and ω 4 ( 13 C), respectively, and (2) the chemical shift values of 1 H α , -1 and 13 C α ,.] are measured in a frequency domain dimension, ω]( 13 C α ), by the frequency difference between the two peaks forming the peak pair and the frequency at the center of the two peaks, respectively. The 3D H,C,(C-TOCSY-CO),N,HN experiment [0055] The present invention also relates to a method of conducting a reduced dimensionality (RD) three-dimensional (3D) H,C,(C-TOCSY-CO),N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having two consecutive amino acid residues, i-1 and i: (1) aliphatic protons of amino acid residue i-1, 1 H ah / -ι; (2) aliphatic carbons of amino acid residue i-1, X3 C ύ . \ ; (3) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N,; and (4) a polypeptide backbone amide proton of amino acid residue i, 1H N ,. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 H all , -1 and l3 C ύ . \ of amino acid residue i-1 are connected to the chemical shift evolutions of 15 N, and 1H N ,- of amino acid residue i, under conditions effective (1) to generate a NMR signal encoding the chemical shifts of 13 C aI V] and 15 N; in a phase sensitive manner in two indirect time domain dimensions, t]( 13 C ah ) and t 2 ( 15 N), respectively, and the chemical shift of 1H N / in a direct time domain dimension, t 3 ( ! H N ), and (2) to cosine modulate the chemical shift evolutions of "C^ M in tι( 13 C a ) with the chemical shift evolutions of 1 H ali . 1 . Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 15 N, and H N ; are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 (1H N ), respectively, and (2) the chemical shift values of 1 H ali -1 and "C^M are measured in a frequency domain dimension, ω]( 13 C ah ), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0056] In addition, the method of conducting a RD 3D H,C,(C-TOCS Y- CO),N,HN NMR experiment can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C a i and 15 N,- in a phase sensitive manner in t]( 13 C a ) and t ( 15 N) and the chemical shift value of 1 ¥J ti i in t 3 (1H N ), and (2) to avoid cosine modulating the chemical shift evolutions of 13 C all ;-1 in tι( I3 C ah ) with the chemical shift evolution of 1H°V.] for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with additional peaks located centrally between two peaks forming the peak pairs which measure the chemical shift values of 13 C ah ;.] along C0]( 13 C ah ). Those additional peaks can be derived from 13 C ah nuclear spin polarization. One specific embodiment (3D HC-(C-TOCSY-CO NHN) of this method is illustrated in Figure IC, where the applying radiofrequency pulses effects a nuclear spin polarization transfer, where a radiofrequency pulse is used to create transverse 'H 81 ' .] magnetization, and 1 H aIl ,-ι magnetization is transferred to 13 C aIl 7- ι, to 13 C α ;-1 , to 13 C'M, to 15 N , and to 1 H N ,-, where the NMR signal is detected. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2C to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2C, where phase φ] of the first ! H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted, whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the peak pairs, and a second NMR subspectrum derived from the adding which contains the additional peaks located centrally between the two peaks forming the peak pairs. [0057] In an alternate embodiment, the RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment can be modified to a RD 2D H,C,(C-TOCSY- CO,N),HN NMR experiment, which involves applying radiofrequency pulses so that the chemical shift evolution of 15 N, does not occur. Then, the NMR signals are processed to generate a two dimensional (2D) NMR spectrum with peak pairs where (1) the chemical shift value of 1 H N ,- is measured in a frequency domain dimension, ω 2 (1H N ), and (2) the chemical shift values of 1 H all , -1 and 13 C all M are measured in a frequency domain dimension, ω]( 13 C ah ), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0058] In an alternate embodiment, the RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment can be modified to a RD 4D H,C,(C- TOCS Y),CO,N,HN NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of a polypeptide backbone carbonyl carbon of ammo acid residue i-1, C',-_ι, occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C' .] in a phase sensitive manner in an indirect time domain dimension, t 4 ( 13 C). Then, the NMR signals are processed to generate a four dimensional (4D) NMR spectrum with variant peak pairs where (1) the chemical shift values of 15 N,, 1H N ,- and 13 C',.ι are measured in three frequency domain dimensions, ω 2 ( 15 N), ω 3 (1H N ), and ω ( 13 C), respectively, and (2) the chemical shift values of 1H all ;-1 and 13 C all / -ι are measured in a frequency domain dimension, C0]( 13 C al1 ), by the frequency differences between the two peaks forming the variant peak pairs and the frequencies at the center of the two peaks, respectively. The 3D H^C^CO-HA experiment [0059] Another aspect of the present invention relates to a method of conducting a reduced dimensionality (RD) three-dimensional (3D) H α β ,C α β ,CO,HA nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having an amino acid residue, i: (1) a β-proton of amino acid residue i, 1H β ,; (2) a β-carbon of amino acid residue i, 13 C β -; (3) an α-proton of amino acid residue i, 1H α ; (4) an α-carbon of amino acid residue i, 13 C α ,; and (5) a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1H α , 1H β ;, 13 C α ,-, and 13 C β , are connected to the chemical shift evolution of 13 C' / , under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α ,-, 13 C β , and 13 C',- in a phase sensitive manner in two indirect time domain dimensions, t]( 13 C β ) and t 2 ( 13 C), respectively, and the chemical shift value of ] H α in a direct time domain dimension, t 3 (1H α ), and (2) to cosine modulate the chemical shift evolutions of 13 C α ,- and I3 C β ,- in t]( 13 C α β ) with the chemical shift evolutions of 1 H I - and 1H P /, respectively. Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 13 C\- and 1H α ; are measured in two frequency domain dimensions, ω 2 ( 13 C) and ω 3 ( 1 H α ), respectively, and (2) (i) the chemical shift values of 1H α ,- and 1H β ,- are measured in a frequency domain dimension, ω 1 ( 13 C α/β ), by the frequency differences between the two peaks forming the peak pairs, and (ii) the chemical shift values of 13 C α ,-, and 13 C β ,- are measured in a frequency domain dimension, cθ]( 13 C α/β ), by the frequencies at the center of the two peaks forming the peak pairs. [0060] In addition, the method of conducting a RD 3D H α β ,C α β ,CO,HA NMR experiment can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α 5 13 C β , and 15 N,- in a phase sensitive manner in t^C^) and t 2 ( 15 N) and the chemical shift value of 1H* in t 3 ( 1 H α ), and (2) to avoid cosine modulating the chemical shift evolutions of 13 C α ; - and 13 C β , in t]( 13 C α/β ) with the chemical shift evolutions of 1 H ,- and 'H 13 ,- for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with additional peaks located centrally between two peaks forming the peak pairs which measure the chemical shift values of 13 C" and 13 C β ; - along ω]( 13 C α β ). Those additional peaks can be derived from 13 C α and 13 C β nuclear spin polarization. One specific embodiment (3D H α/β C α β COHA) of this method is illustrated in Figure IE, where the applying radiofrequency pulses effects a nuclear spin polarization transfer, where a radiofrequency pulse is used to create transverse 1H α ,- and ! H β magnetization, and 1H α ; and 1 H β ; - polarization is transferred to 13 C α , and 13 C β ,-, to 13 C' , and back to 1H α , where the NMR signal is detected. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2E to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2E, where phase φ] of the first 1H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted, whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the peak pairs, and a second NMR subspectrum derived from the adding which contains the additional peaks located centrally between the two peaks forming the peak pairs. [0061] In an alternate embodiment, the RD 3D H α p £ α p ,CO,HA NMR experiment can be modified to a RD 2D H α/β ,C α/β ,(CO),HA NMR experiment, which involves applying radiofrequency pulses so that the chemical shift evolution of C, does not occur. Then, the NMR signals are processed to generate a two dimensional (2D) NMR spectrum with peak pairs where (1) the chemical shift value of 1 H α ,- is measured in a frequency domain dimension, ω 2 (1H ), and (2) (i) the chemical shift values of 1H α ; and 1H β ,- are measured in a frequency domain dimension, CD]( 13 C α β ), by the frequency differences between two peaks forming the peak pairs, respectively, and (ii) the chemical shift values of 13 C α ,, and 13 C β ; are measured in a frequency domain dimension, ω 1 ( 13 C α β ), by the frequencies at the center of the two peaks forming the peak pairs. The 3D H α/β ,C α/β ,N,HN experiment [0062] A further aspect of the present invention relates to a method of conducting a reduced dimensionality (RD) three-dimensional (3D) H tx/β ,C α/β ,N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having an amino acid residue, i: (1) a β-proton of amino acid residue i, 'H 13 ,; (2) a β-carbon of amino acid residue i, 13 C β ,; (3) an α-proton of amino acid residue i, 1H α ,-; (4) an α-carbon of amino acid residue i, 13 C α ;; (5) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N,; and (6) a polypeptide backbone amide proton of amino acid residue i, 1H N ; -. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1H α ; -, 1H 13 , 13 C α ; , and 13 C β , are connected to the chemical shift evolutions of 15 N, and 1H N , under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C" , 13 C β ,- and 15 N,- in a phase sensitive manner in two indirect time domain dimensions, t 1 ( 13 C α β ) and t ( I5 N), respectively, and the chemical shift value of 1 H N , in a direct time domain dimension, t 3 ( ! H N ), and (2) to cosine modulate the chemical shift evolutions of 13 C α and 13 C β ,- in t 1 ( 13 C α/β ) with the chemical shift evolutions of 1H α ,- and 1 H β ,-, respectively. Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 15 N,- and 'H 1 ^,- are measured in two frequency domain dimensions, ω ( 15 N) and ω 3 (1H N ), respectively, and (2) (i) the chemical shift values of 1H α and 1H β / are measured in a frequency domain dimension, ωι( 13 C α β ), by the frequency differences between the two peaks forming the peak pairs, and (ii) the chemical shift values of 13 C ,, and 13 C β ,- are measured in a frequency domain dimension, ω 1 ( 13 C α β ), by the frequencies at the center of the two peaks forming the peak pairs. [0063] In addition, the method of conducting a RD 3D H α/β ,C α/β ,N,HN NMR experiment can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α ,-, 13 C β ,- and 15 N,- in a phase sensitive manner in fι( 13 C α p ) and t 2 ( 15 N) and the chemical shift value of 1H N , in t 3 (1H N ), and (2) to avoid cosine modulating the chemical shift evolutions of 13 C α ,- and 13 C β ,- in tι( 13 C a ) with the chemical shift evolutions of 'H", and 1H β , for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with additional peaks located centrally between two peaks forming the peak pairs which measure the chemical shift values of 13 C α ,- and 13 C β ,- along ω ι( l3 C a ). Those additional peaks can be derived from 13 C α and 13 C β nuclear spin polarization. One specific embodiment (3D H β C α β NHN) of this method is illustrated in Figure IF, where the applying radiofrequency pulses effects a nuclear spin polarization transfer where a radiofrequency pulse is used to create transverse 1 H α ,- and 1H β ; magnetization, and 1 H α ,- and 1H β , magnetization is transferred to 13 C α ,- and 13 C β ; -, to 15 N„ and to 1H N ,-, where the NMR signal is detected. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2F to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2F, where phase φj of the first ! H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted, whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the peak pairs, and a second NMR subspectrum derived from the adding which contains the additional peaks located centrally between the two peaks forming the peak pairs. [0064] In an alternate embodiment, the RD 3D H α/β ,C α/β ,N,HN NMR experiment can be modified to a RD 2D H α/β ,C β ,(N),HN NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of N; does not occur. Then, the NMR signals are processed to generate a two dimensional (2D) NMR spectrum with peak pairs where (1) the chemical shift value of 1H N is measured in a frequency domain dimension, ω 2 (1H N ), and (2) (i) the chemical shift values of 1H α ,- and 1H β ,- are measured in a frequency domain dimension, a)i( 13 C ot/p ), by the frequency differences between the two peaks forming the peak pairs, and (ii) the chemical shift values of 13 C α ,-, and 13 C β ; - are measured in a frequency domain dimension, ω 1 ( 13 C α/β ), by the frequencies at the center of the two peaks forming the peak pairs. The 3D H,C,C,H-COSY experiment [0065] The present invention also relates to a method of conducting a reduced dimensionality (RD) three-dimensional (3D) H,C,C,H-COSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1 H m , 13 C m , 1H", and 13 C" of a protein molecule where m and n indicate atom numbers of two CH, CH 2 or CH 3 groups that are linked by a single covalent carbon-carbon bond in an amino acid residue. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 H m and 13 C m are connected to the chemical shift evolutions of 1H" and 13 C", under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C W and 13 C" in a phase sensitive manner in two indirect time domain dimensions, t ϊ ( 13 C ) and t 2 ( 13 C"), respectively, and the chemical shift value of 1H" in a direct time domain dimension, t 3 (1H"), and (2) to cosine modulate the chemical shift evolution of 13 C m in tι( 13 C") with the chemical shift evolution of 1H m . Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 13 C" and 1H" are measured in two frequency domain dimensions, ω 2 ( 13 C") and ω 3 (1H"), respectively, and (2) the chemical shift values of 1H'" and 13 C" are measured in a frequency domain dimension, ωι( 13 C"), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0066] In addition, the method of conducting a RD 3D H,C,C,H-COS Y NMR experiment can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of l3 C m and 13 C" in a phase sensitive manner in tι( 13 C m ) and t 2 ( 13 C") and the chemical shift value of ! H" in t 3 (1H), and (2) to avoid cosine modulating the chemical shift evolution of 13 C m in tι( 13 C m ) with the chemical shift evolution of 1 H™ for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with additional peaks located centrally between two peaks forming the peak pairs which measure the chemical shift value of 13 C ra along ωι( 13 C w ). Those additional peaks can be derived from 13 C m nuclear spin polarization. One specific embodiment (3D HCCH-COSY) of this method is illustrated in Figure IH, where the applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IH, where a radiofrequency pulse is used to create transverse 1 K m magnetization, and 1 H W magnetization is transferred to 13 C", to 13 C", and to 1H", where the NMR signal is detected. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2H to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2H, where phase φ] of the first 1H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted, whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the peak pairs, and a second NMR subspectrum derived from the adding which contains the additional peaks located centrally between the two peaks forming the peak pairs. [0067] In an alternate embodiment, the RD 3D H,C,C,H-COS Y NMR experiment can be modified to a RD 2D H,C,(C),H-COSY NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of 13 C" does not occur. Then, the NMR signals are processed to generate a two dimensional (2D) NMR spectrum with peak pairs where (1) the chemical shift value of 1H" is measured in a frequency domain dimension, co 2 (1H"), and (2) the chemical shift values of l Jϋ m and 13 C" are measured in a frequency domain dimension, ωι( 13 C w ), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. The 3D H,C,C,H-TOCSY experiment [0068] Another aspect of the present invention relates to a method of conducting a reduced dimensionality (RD) three-dimensional (3D) H,C,C,H- TOCS Y nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1 H m , 13 C m , 1H", and 13 C" of a protein molecule where m and n indicate atom numbers of two CH, CH 2 or CH 3 groups that may or may not be linked by a single covalent carbon-carbon bond in an amino acid residue. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1H W and 13 C m are connected to the chemical shift evolutions of ! H" and 13 C", under conditions effective (1) to generate NMR signals encoding the chemical shift values of I3 C" and 13 C" in a phase sensitive manner in two indirect time domain dimensions, tι( 13 ") and t ( 13 C"), and the chemical shift value of 1H" in a direct time domain dimension, t 3 ( ! H"), and (2) to cosine modulate the chemical shift evolution of 13 C in tι( 13 C") with the chemical shift evolution of 1 H"'. Then, the NMR signals are processed to generate a 3D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift values of 13 C" and 1H" are measured in two frequency domain dimensions, ω 2 ( 13 C") and ω 3 (1H"), respectively, and (2) the chemical shift values of 1 Jϊ m and 13 C" are measured in a frequency domain dimension, coι( 13 C"), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0069] In addition, the method of conducting a RD 3D H,C,C,H-TOCS Y NMR can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C" and 13 C" in a phase sensitive manner in t 1 ( 13 C w ) and t 2 ( 13 C") and the chemical shift value of 1H" in t 3 (1H"), and (2) to avoid cosine modulating the chemical shift evolution of 13 C m in tι( 13 C m ) with the chemical shift evolution of l \ for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 3D NMR spectrum with additional peaks located centrally between two peaks forming the peak pairs which measure the chemical shift value of 13 C ra along ω 1 ( 13 C" ! ). Those additional peaks can be derived from 13 C" nuclear spin polarization. One specific embodiment (3D HCCH-TOCSY) of this method is illustrated in Figure II, where the applying radiofrequency pulses effects a nuclear spin polarization transfer where a radiofrequency pulse is used to create transverse 1H" 1 magnetization, and 1 H m magnetization is transferred to l3 C m , to 13 C", and to 1H", where the NMR signal is detected. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 21 to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 21, where phase φi of the first 1H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted, whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the peak pairs, and a second NMR subspectrum derived from the adding which contains the additional peaks located centrally between the two peaks forming the peak pairs. [0070] In an alternate embodiment, the RD 3D H,C,C,H-TOCSY NMR experiment can be modified to a RD 2D H,C,(C),H-TOCS Y NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of 13 C" does not occur. Then, the NMR signals are processed to generate a two dimensional (2D) NMR spectrum with peak pairs where (1) the chemical shift value of 1H" is measured in a frequency domain dimension, ω 2 (1H"), and (2) the chemical shift values of ! H m and l3 " are measured in a frequency domain dimension, ωι( 13 C"), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. The 2D HB,CB,(CG,CD),HD experiment [0071] A further aspect of the present invention relates to a method of conducting a reduced dimensionality (RD) two-dimensional (2D) HB,CB,(CG.CD).HD nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule: (1) a β-proton of an amino acid residue with an aromatic side chain, 1H β ; (2) a β- carbon of an amino acid residue with an aromatic side chain, 13 C β ; and (3) a δ- proton of an amino acid residue with an aromatic side chain, H . The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1H β and 13 C β are connected to the chemical shift evolution of 1H δ , under conditions effective (1) to generate NMR signals encoding the chemical shift value of 13 C β in a phase sensitive manner in an indirect time domain dimension, tι( 13 C β ), and the chemical shift value of 1H δ in a direct time domain dimension, t^H 5 ), and (2) to cosine modulate the chemical shift evolution of 13 C β in t ! ( 13 C p ) with the chemical shift evolution of 1H β . Then, the NMR signals are processed to generate a 2D NMR spectrum with a peak pair derived from the cosine modulating where (1) the chemical shift value of H is measured in a frequency domain dimension, ω 2 ( H ), and (2) the chemical shift values of 1H β and 13 C β are measured in a frequency domain dimension, ω ϊ ( 13 C β ), by the frequency difference between the two peaks forming the peak pair and the frequency at the center of the two peaks, respectively. [0072] In addition, the method of conducting a RD 2D HB,CB,(CG,CD),HD NMR experiment can involve applying radiofrequency pulses under conditions effective (1) to generate an additional NMR signal encoding the chemical shift value of 13 C β in a phase sensitive manner in tι( 13 C p ) and the chemical shift value of 1H δ in t^H 8 ), and (2) to avoid cosine modulating the chemical shift evolution of 13 C β in t ! ( I3 C β ) with the chemical shift evolution of W for the additional NMR signal. Then, the NMR signals and the additional NMR signal are processed to generate a 2D NMR spectrum with an additional peak located centrally between the two peaks forming the peak pair which measure the chemical shift value of 13 C β along cθ!( 13 C). That additional peak can be derived from 13 C β nuclear spin polarization. One specific embodiment (2D HBCB(CGCD)HD) of this method is illustrated in Figure 1 J, where the applying radiofrequency pulses effects a nuclear spin polarization transfer where a radiofrequency pulse is used to create transverse 1H β magnetization, and H β magnetization is transferred to 13 C β , to 13 C δ , and to 1H δ , where the NMR signal is detected. Another specific embodiment of this method involves applying radiofrequency pulses by (1) applying a first set of radiofrequency pulses according to the scheme shown in Figure 2 J to generate a first NMR signal, and (2) applying a second set of radiofrequency pulses according to the scheme shown in Figure 2J, where phase φ t of the first 1H pulse is altered by 180° to generate a second NMR signal. Then, prior to the processing, the first NMR signal and the second NMR signal are added and subtracted, whereby the NMR signals are processed to generate a first NMR subspectrum derived from the subtracting which contains the peak pair, and a second NMR subspectrum derived from the adding which contains the additional peak located centrally between the two peaks forming the peak pair. [0073] In an alternate embodiment, the RD 2D HB,CB,(CG,CD),HD NMR experiment can be modified to a RD 3D HB,CB,(CG),CD,HD NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of a δ-carbon of an amino acid residue with an aromatic side chain, 13 C δ occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C δ in a phase sensitive manner in an indirect time domain dimension, t 3 ( 13 C δ ). Then, the NMR signals are processed to generate a three dimensional (3D) NMR spectrum with a peak pair where (1) the chemical shift values of H and C are measured in two frequency domain dimensions, ω 2 ( H ) and ω 3 ( 13 C δ ), respectively, and (2) the chemical shift values of 1H β and 13 C β are measured in a frequency domain dimension, ω ! ( 13 C β ), by the frequency difference between the two peaks forming the peak pair and the frequency at the center of the two peaks, respectively. [0074] In an alternate embodiment, the RD 2D HB,CB,(CG,CD),HD NMR experiment can be modified to a RD 3D HB,CB,CG,(CD),HD NMR experiment which involves applying radiofrequency pulses so that the chemical shift evolution of a γ-carbon of an amino acid residue with an aromatic side chain, 13 C γ occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C γ in a phase sensitive manner in an indirect time domain dimension, t 3 ( 13 C γ ), and said processing the NMR signals generates a three dimensional (3D) NMR spectrum with a peak pair wherein (1) the chemical shift values of 1H δ and 13 C γ are measured in two frequency domain dimensions, ω 2 (1H δ ) and ω 3 ( 13 C γ ), respectively, and (2) the chemical shift values of 1H β and 13 C β are measured in a frequency domain dimension, ω ! ( 13 C β ), by the frequency difference between the two peaks forming said peak pair and the frequency at the center of the two peaks, respectively. The 2D H,C,H-COS Y experiment [0075] The present invention also relates to a method of conducting a reduced dimensionality (RD) two-dimensional (2D) H,C,H-COSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for l H m , 13 C", and ! H" of a protein molecule where m and n indicate atom numbers of two CH, CH or CH 3 groups in an amino acid residue. The method involves providing a protein sample and applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer where the chemical shift evolutions of 1 U m and 13 C m are connected to the chemical shift evolution of 1H", under conditions effective (1) to generate NMR signals encoding the chemical shift value of 13 C m in a phase sensitive manner in an indirect time domain dimension, tι( 13 C m ), and the chemical shift value of 1H" in a direct time domain dimension, t 2 (1H"), and (2) to cosine modulate the chemical shift evolution of 13 C in fι( 13 C") with the chemical shift evolution of 1H m . Then, the NMR signals are processed to generate a 2D NMR spectrum with peak pairs derived from the cosine modulating where (1) the chemical shift value of 1H" is measured in a frequency domain dimension, ω 2 (1H"), and (2) the chemical shift values of 1H OT and l3 C m are measured in a frequency domain dimension, ωι( 13 C"), by the frequency differences between the two peaks forming the peak pairs and the frequencies at the center of the two peaks, respectively. [0076] One specific embodiment (2D 1H-TOCSY-HCH-COSY) of this method is illustrated in Figure IK, where the applying radiofrequency pulses effects a nuclear spin polarization transfer where a radiofrequency pulse is used to create transverse ! H m magnetization, and Η m polarization is transferred to 13 C™, to 1 H m , and to 1H", where the NMR signal is detected. Although the specific embodiment illustrated in Figure IK shows this method applied to an amino acid residue with an aromatic side chain, this method also applies to amino acid residues with aliphatic side chains. Another specific embodiment of this method involves applying radiofrequency pulses according to the scheme shown in Figure 2K. [0077] Figure 3 outlines which chemical shifts are correlated in the various NMR experiments described above. Combinations of RD NMR Experiments [0078] Accordingly, a suite of multidimensional RD NMR experiments enables one to devise strategies for RD NMR-based HTP resonance assignment of proteins. [0079] Thus, another aspect of the present invention relates to a method for sequentially assigning chemical shift values of an α-proton, 1H α , an α-carbon, 13 C α , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1 H N ' of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D HA,CA,(CO),N,HN NMR experiment to measure and connect chemical shift values of the α-proton of amino acid residue i-1, l H a j.ι, the α-carbon of amino acid residue i-1, 13 C α ;- ι, the polypeptide backbone amide nitrogen of amino acid residue i, 15 N 7 , and the polypeptide backbone amide proton of amino acid residue i, 1H N ,- and (2) a RD 3D HNNCAHA NMR experiment to measure and connect the chemical shift values of the α-proton of amino acid residue i, 1 H α ,-, the α-carbon of amino acid residue i, 13 C α ,-, 15 N,-, and 1H N ,. Then, sequential assignments of the chemical shift values of 1H α , 13 C , 15 N, and 1H N are obtained by (i) matching the chemical shift values of 'H" - ! and 13 C !-1 with the chemical shift values of 'H" and 13 C"-, (ii) using the chemical shift values of 1 H , -1 and 13 C α ;-1 to identify the type of amino acid residue i-1 (Wϋthrich, NMR of Proteins and Nucleic Acids. Wiley, New York (1986); Grzesiek et al., J. Biomol. NMR. 3: 185-204 (1993), which are hereby incoφorated by reference in their entirety), and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements (such as α-helices and β-sheets) within the polypeptide chain (Spera et al., J. Am. Chem. Soc. 113:5490-5492 (1991); Wishart et al., Biochemistry, 31:1647-1651, which are hereby incoφorated by reference in their entirety). [0080] In one embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' ;-1 , 13 C α ,, 15 N , and 'H**,-. Then, sequential assignments of the chemical shift value of C' ;-1 , are obtained by matching the chemical shift value of 13 C α . measured by the RD 3D HNN<CO,CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by the RD 3D HA,CA,(CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment. [0081] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to (i) a RD 3D H α β ,C α/β ,CO,HA NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1 H β ,-, the β-carbon of amino acid residue i, 13 C β ,-, the α-proton of amino acid residue i, 1H α ;, the α-carbon of amino acid residue i, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',-, and (ii) a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of 13 C',-, the α-carbon of amino acid residue i+1, 13 C α /+ ι, the polypeptide backbone amide nitrogen of amino acid residue i+1, 15 N, +1 , and the polypeptide backbone amide proton of amino acid residue i+1, Then, sequential assignments are obtained by matching the chemical shift value of C, measured by the RD 3D HNN<CO.CA> NMR experiment with the chemical shift value of 13 C',- measured by the RD 3D H α/β ,C α/β ,CO,HA NMR experiment. [0082] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of aliphatic protons (including α-, β-, and γ-protons) of amino acid residue i-1, 1 H al, ,_ 1 , aliphatic carbons (including α-, β-, and γ-carbons) of amino acid residue i-1, 13 C ah r-1 , 15 N,-, and 1H N ,-. Then, sequential assignments of the chemical shift values of 1 H all ,-.ι and ^C 3 " 1 ,-! for amino acid residues i having unique pairs of 15 N,- and 1 H N , chemical shift values are obtained by matching the chemical shift values of 'H* and 13 C measured by said RD 3D HNNCAHA NMR experiment and RD 3D HA,CA,(CO),N,HN NMR experiment with the chemical shift values of 'H",. ! and 13 C α M measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and using the 1 H al, ,_ 1 and 13 C ah j.ι chemical shift values to identify the type of amino acid residue i-1. [0083] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of 'H 3 ' 1 ,- and 13 C ah ; of amino acid residue i. Then, sequential assignments of the chemical shift values of 1H aIl ; - and 13 C al1 ,-, the chemical shift values of a γ-proton, 'H',, and a γ-carbon, 13 C γ , in particular, are obtained by (i) matching the chemical shift values of 1H α ,- and 13 C α , measured using the RD 3D H,C,C,H-COS Y NMR experiment or the RD 3D H,C,C,H-TOCSY RD NMR experiment with the chemical shift values of 1H α and 13 C α measured by the RD 3D HA,CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α β C /β (CO)NHN NMR experiment and (ii) using the chemical shift values of 1H al1 and 13 C ah , the chemical shift values of 1H γ ,- and I3 C γ , in particular, to identify the type of amino acid residue i. [0084] In yet another embodiment, this method involves, in addition to the RD 3D HA.CA.(CO).N.HN NMR experiment and the RD 3D HNNCAHA NMR experiment, further subjecting the protein sample to a RD 3D H α β C α/β (CO)NHN NMR experiment to measure and connect the chemical shift values of the β- proton of amino acid residue i-1, 1H β / -ι, the β-carbon of amino acid residue i-1, 13 C P M, ^M, 13 C α M , 15 N;, and 1H N ,-. Then, sequential assignments of the chemical shift values of ! H β and 13 C β are obtained by using the chemical shift values of 1 H β ,-ι and to identify the type of amino acid residue i-1. [0085] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α/β C α/β (CO)NHN NMR experiment, be further subjected to a RD 3D H^-C^CO-HA NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1 H β ,-, the β- carbon of amino acid residue i, 13 C β ,-, 1 H α ,-, 13 C α ; -, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',-. Then, sequential assignments of the chemical shift value of 13 C\- are obtained by matching the chemical shift values of 1H β /; 13 C β ; -, 1H α 5 and 13 C α ; measured by the RD 3D H α β ,C α/p ,CO,HA NMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N measured by the RD 3D HA,CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α β C α β (CO)NHN NMR experiment. [0086] In another embodiment, the protein sample could, in addition to the RD 3D HA 5 CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α β C α β (CO)NHN NMR experiment, be further subjected to a RD 3D H α/β ,C α/β ,N,HN NMR experiment to measure and connect the chemical shift values of 1H β /5 13 C β /5 1H α , 13 C α ,-, 15 N 5 and 1H N ; -. Then, sequential assignments are obtained by matching the chemical shift values of H β ,-, 13 C β ; -, 1 H α ,-, and 13 C α , with the chemical shift values of 1 H β , -1 , 13 C β M , 1H α M , and 13 C α M measured by the RD 3D H α/β C α β (CO)NHN NMR experiment. [0087] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H oc/β C α β (CO)NHN NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to measure and connect the chemical shift value of 13 C β ,-, 13 C α ,-, 15 N , and 1H N ; . Then, sequential assignments are obtained by matching the chemical shift values of 13 C β , and 13 C α / measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C P ;.ι and 13 C α M measured by the RD 3D H α/β C α/β (CO)NHN NMR experiment. [0088] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α/β C α/β (CO)NHN NMR experiment, be further subjected to a RD 2D HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 1 H β ; -ι, 13 C β ;-1 , and a δ-proton of amino acid residue 7-1 with an aromatic side chain, H ;-1 . Then, sequential assignments are obtained by matching (i) the chemical shift values of 1 H β , -1 and 13 C β ;-1 measured by said RD 2D HB,CB,(CG,CD),HD NMR experiment with the chemical shift values of 1H β and 13 C β measured by the RD 3D H α/β C α/β (CO)NHN NMR experiment, (ii) using the chemical shift values to identify amino acid residue i as having an aromatic side chain, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along the polypeptide chain. [0089] In another embodiment, the protein sample could, in addition to the RD 3D HA,CA,(CO),N,HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α/β C α β (CO)NHN NMR experiment, be further subjected to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H- TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons (including α-, β-, and γ-protons) of amino acid residue i, 1 H ah ,, and aliphatic carbons (including α-, β-, and γ-carbons) of amino acid residue i, 13 C ',-, of amino acid residue i. Then, sequential assignments of the chemical shift values of 1 H ah ,- and 13 C ah ,, the chemical shift values of a γ-proton, 1 H y , and a γ- carbon, 13 C γ , in particular, are obtained by (i) matching the chemical shift values of 1H β 5 13 C β 3 1 H α , and 13 C α , measured using the RD 3D H,C,C,H-COSY NMR experiment or the RD 3D H,C,C,H-TOCSY RD NMR experiment with the chemical shift values of 1H β ,-, 13 C β ,-, 'H 01 ,-, and 13 C α ; measured by the RD 3D HA.CA.(CO .N.HN NMR experiment, the RD 3D HNNCAHA NMR experiment, and the RD 3D H α/β C α/β (CO)NHN NMR experiment and (ii) using the chemical shift values of 1H ali and 13 C ali , the chemical shift values of 1H γ and 13 C γ in particular, to identify the type of amino acid residue i. [0090] Yet another aspect of the present invention relates to a method for sequentially assigning chemical shift values of a β-proton, 1H β , a β-carbon, I3 C β , an α-proton, 1 H α , an α-carbon, 13 C α , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 'H 1 " 1 , of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D H α/β C α/β (CO)NHN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i-1, 1H P / -ι, the β-carbon of amino acid residue i-1, 13 C β ,.ι, the α-proton of amino acid residue i-1, 1H α .ι, the α-carbon of amino acid residue i-1, 13 C ,-.ι, the polypeptide backbone amide nitrogen of amino acid residue i, 15 N , and the polypeptide backbone amide proton of amino acid residue i, 1H N ; and (2) a RD 3D H α/β ,C α β ,N,HN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1H β ; -, the β-carbon of amino acid residue i, 13 C β ,-, the α-proton of amino acid residue i, 'H"-, the α-carbon of amino acid residue i, 13 C α ,-, 15 N,-, and 1 l N j. Then, sequential assignments of the chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N are obtained by (i) matching the chemical shift values of the α- and β-protons of amino acid residue i-1, 1H α/|3 ,-.ι, and the chemical shift values of the α- and β-carbons of amino acid residue i-1, "C^i, with 'H 0 ^ and ^C^,-, (ii) using 1 H α p M and 13 C α/β to identify the type of amino acid residue i-1 (Wϋthrich, NMR of Proteins and Nucleic Acids. Wiley, New York (1986); Grzesiek et al., J. Biomol. NMR. 3 : 185-204 (1993), which are hereby incoφorated by reference in their entirety), (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain (Spera et al., J. Am. Chem. Soc, 113:5490-5492 (1991); Wishart et al., Biochemistry, 31:1647-1651, which are hereby incoφorated by reference in their entirety). [0091] In one embodiment, the protein sample could, in addition to the RD 3D H α β C α/β (CO)NHN NMR experiment and the RD 3D H α/β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 3D HA,CA,(CO),N,HN NMR experiment (i) to measure and connect chemical shift values of 1 H".ι, 13 C α (-1 , 15 N;, and 1H N ,- and (ii) to distinguish between NMR signals for 1H°7 13 C α and 1H β / 13 C β measured in the RD 3D H α/β C α β (CO)NHN NMR experiment and the RD 3D H α p ,C α/p ,N,HN NMR experiment. [0092] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 3D H α β ,C α/β ,CO,HA NMR experiment to measure and connect the chemical shift values of 1 H β ,-, 13 C β ,-, 1 H α ,-, 13 C"-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',-. Then, sequential assignments of the chemical shift value of 13 C' ; are obtained by matching the chemical shift values of 1 H β / -, 13 C β ; -, 1 H α ,-, and 13 C α , measured by the RD 3D H α/β ,C α β ,CO,HA NMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N measured by the RD 3D H α β C α/β (CO)NHN NMR experiment and the RD 3D H ct/β ,C α β ,N,HN NMR experiment. [0093] In another embodiment, the protein sample could, in addition to the RD 3D H α β C α/β (CO)NHN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' M , 13 C α ,-, 15 N,-, and 1 H N ,-. Then, sequential assignments of the chemical shift value of 13 C' ;-1 are obtained by matching the chemical shift value of 13 C" measured by the RD 3D HNN<CO,CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by the RD 3D H α/β C α/β (CO)NHN NMR experiment and RD 3D H α/β ,C α β ,N,HN NMR experiment. [0094] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment and the RD 3D H α/β ,C α/β ,N,HN NMR experiment, be further subjected to (i) a RD 3D If^C^COLIA NMR experiment to measure and connect the chemical shift values of 1H 13 ,-, 13 C β ,, 1 H α ,, 13 C α ;, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',- and (ii) a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of 13 C',-, the α-carbon of amino acid residue i+1, 13 C α +l5 the polypeptide backbone amide nitrogen of amino acid residue i+1, 15 N +l3 and the polypeptide backbone amide proton of amino acid residue i+1, 1 H N ; +1 . Then, sequential assignments are obtained by matching the chemical shift value of 13 C, measured by said RD 3D HNN<CO,CA> NMR experiment with the chemical shift value of 13 C',- measured by the RD 3D H α β ,C α β ,CO,HA NMR experiment. [0095] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α β (CO)NHN NMR experiment and the RD 3D H α β ,C α β ,N,HN NMR experiment, be further subjected to a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of 1H ah / -ι. 13 C ah M , 15 N,-, and 1 j i i . Then, sequential assignments of the chemical shift values of I H all !-1 and 13 C a 'Vι for amino acid residues i having unique pairs of 15 N; and 1H N chemical shift values are obtained by matching the chemical shift values of 1H β , 13 C β , 1H α , and I3 C α measured by the RD 3D H α β C α β (CO)NHN NMR experiment and RD 3D H β ,C α/β ,N,HN NMR experiment with the chemical shift values of 1H P M , 13 C β , 'tf i, and 13 C α r-1 measured by the RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment and using the 1 H ali /-1 and 13 C aU chemical shift values to identify the type of amino acid residue i-1. [0096] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment and the RD 3D H^C^HHN NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to measure and connect the chemical shift value of 13 C β ,-, 13 C α ,-, I5 N,-, and 1H N . Then, sequential assignments are obtained by matching the chemical shift values of 13 C β , and 13 C" measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β and 13 C α M measured by the RD 3D H α/β C α/β (CO)NHN NMR experiment. [0097] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α β (CO)NHN NMR experiment and the RD 3D H α β ,C α β ,N,HN NMR experiment, be further subjected to a RD 2D HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 'H 13 ,-, 13 C β ,-, and a δ-proton of amino acid residue i with an aromatic side chain, H ,-. Then, sequential assignments are obtained by (i) matching the chemical shift values of 1 H β and 13 C P , measured by said RD 2D HB,CB,(CG,CD),HD NMR experiment with the chemical shift values of 1H P and 13 C P measured by the RD 3D H α/β C α β (CO)NHN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, (ii) using the chemical shift values to identify amino acid residue i as having an aromatic side chain, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along the polypeptide chain (Spera et al., J. Am. Chem. Soc. 113:5490-5492 (1991); Wishart et al., Biochemistry, 31:1647-1651, which are hereby incoφorated by reference in their entirety). [0098] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α β (CO)NHN NMR experiment and the RD 3D H α β ,C α β ,N,HN NMR experiment, be further subjected to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, l U aU i, and aliphatic carbons of amino acid residue i, 13 C al1 ,-, of amino acid residue i. Then, sequential assignments of the chemical shift values of 1H al1 ,- and 13 C a1 ',-, the chemical shift values of a γ-proton, ^j, and a γ-carbon, 13 C γ , in particular, are obtained by (i) matching the chemical shift values of W, 13 C β ,-, l JΛ α and 13 C α , measured using the RD 3D H,C,C,H-COSY NMR experiment or the RD 3D H,C,C,H-TOCSY RD NMR experiment with the chemical shift values of 1H β , 13 C P , 1 H α , and 13 C α measured by the RD 3D H α/β C α/β (CO)NHN NMR experiment and the RD 3D H α β ,C α β ,N,HN NMR experiment, and (ii) using the chemical shift values of 'H 3 ' 1 ,- and 13 C ali ,.the chemical shift values of 1H γ ,- and 13 C γ ; - in particular, to identify the type of amino acid residue i. [0099] A further aspect of the present invention involves a method for sequentially assigning the chemical shift values of aliphatic protons, 1 H ah , aliphatic carbons, 13 C ah , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N ' of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of the aliphatic protons of amino acid residue i-1, 1 H all , -1 , the aliphatic carbons of amino acid residue i-1, 13 C al ', -1 , the polypeptide backbone amide nitrogen of amino acid residue i, 15 N,-, and the polypeptide backbone amide proton of amino acid residue i, 1H N , and (2) a RD 3D H α β ,C α β ,N,HN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1H β / , the β- carbon of amino acid residue i, 13 C β ,, the α-proton of amino acid residue i, 1H α , the α-carbon of amino acid residue i, 13 C α ;, 15 N,-, and 1 H N / . Then, sequential assignments of the chemical shift values of 1 H ah , 13 C a , 15 N, and 1H N are obtained by (i) matching the chemical shift values of the α- and β-protons of amino acid residue i-1, 'H" 713 ,-.] and the α- and β-carbons of amino acid residue i-1, with the chemical shift values of 'H"^- and 13 C α/β , of amino acid residue i, (ii) using the chemical shift values of I H a ,_ι and 13 C a,I - 1 to identify the type of amino acid residue i-1 (Wϋthrich, NMR of Proteins and Nucleic Acids. Wiley, New York (1986); Grzesiek et al., J. Biomol. NMR. 3 : 185-204 (1993), which are hereby incoφorated by reference in their entirety), and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain (Spera et al., J. Am. Chem. Soc. 113:5490-5492 (1991); Wishart et al., Biochemistry, 31:1647-1651, which are hereby incoφorated by reference in their entirety). [0100] In one embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α/β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 3D H α/β ,C α/β ,CO,HA NMR experiment to measure and connect the chemical shift values of 1H 13 / , 13 C β ,, 1 H α ,, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C' ; . Then, sequential assignments of the chemical shift value of C',- are obtained by matching the chemical shift values of 1H β ; -, 13 C β ,-, 'H",-, and 13 C α ; - measured by the RD 3D H α/β ,C α/β ,CO,HANMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N measured by the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment and the RD 3D H α/β ,C α β ,N,HN NMR experiment. [0101] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C',-. i, 13 C α ,, 15 N,-, and 1H N ,-. Then, sequential assignments of the chemical shift value of 13 C' are obtained by matching the chemical shift value of 13 C α ,- measured by the RD 3D HNN<CO,CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by the RD 3D H,C,(C- TOCSY-CO),N,HN NMR experiment and the RD 3D H α/β ,C α β ,N,HN NMR experiment. [0102] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, be further subjected to (i) a RD 3D H /p ,C α/p ,CO,HA NMR experiment to measure and connect the chemical shift values of 1H β ,-, 13 C β ,-, 1H α ;, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C' / , and (ii) a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of 13 C',-, the α-carbon of amino acid residue i+1, 13 C α r+b the polypeptide backbone amide nitrogen of amino acid residue i+1, 15 N, +1 , and the polypeptide backbone amide proton of amino acid residue i+1, 1 H N , +1 . Then, sequential assignments are obtained by matching the chemical shift value of 13 C',- measured by the RD 3D HNN<CO,CA> NMR experiment with the chemical shift value of 13 C 7 - measured by the RD 3D H α β ,C α/β ,CO,HA NMR experiment. [0103] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α/β ,C α β ,N,HN NMR experiment, be further subjected to a RD 3D H β C α β (CO)NHN NMR experiment (i) to measure and connect the chemical shift values of 'H^ M , 13 C α/β ;-1 , 15 N , and 1H N ; -, and (ii) to identify NMR signals for 15 N,-, and 1H N ,- in the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0104] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α/β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 3D HA,CA,(CO),N,HN NMR experiment (i) to measure and connect chemical shift values of 1H α , 13 C α M , 15 N„ and 1H N ,- and (ii) to identify NMR signals for 1H α and 13 C α in the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α/β ,C α β ,N,HN NMR experiment. [0105] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to measure and connect the chemical shift value of 13 C β ,, 13 C ,-, 15 N,-, and 1H N ,-. Then, sequential assignments are obtained by matching the chemical shift values of 13 C β ,- and 13 C α / measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β /-1 and I3 C α measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0106] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α β ,C α/β ,N,HN NMR experiment, be further subjected to a RD 2D HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 1H 13 , 13 C β , and a δ-proton of amino acid residue i with an aromatic side chain, H ,-. Then, sequential assignments are obtained by matching the chemical shift values of 1 H β / and 13 C β ; measured by said RD 2D HB,CB,(CG,CD)ND NMR experiment with the chemical shift values of 1H β and 13 C β measured by the RD 3D H α/β ,C α/β ,N,HN NMR experiment and the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, using the chemical shift values to identify amino acid residue i as having an aromatic side chain, and mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along the polypeptide chain. [0107] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D H α β ,C α β ,N,HN NMR experiment, be further subjected to a RD 3D H,C,C,H- COSY NMR experiment or a RD 3D H,C,C,H-TOCS Y NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, 'H 3 ' 1 ,-, and aliphatic carbons of amino acid residue i, 13 C al1 ,-. Then, sequential assignments of the chemical shift values of 'H 3 ' 1 ,- and 13 C ah , the chemical shift values of a γ-proton, and a γ-carbon, 13 C γ ,-, in particular, are obtained by (i) matching the chemical shift values of 1 H ah ; and 13 C ah ,- measured using the RD 3D H,C,C,H-COSY NMR experiment or the RD 3D H,C,C,H- TOCS Y NMR experiment with the chemical shift values of 1H ali and 13 C ali measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D H α/p ,C β ,N,HN NMR experiment, and (ii) using the chemical shift values of Η 3 " / and 13 C aIi ; -, the chemical shift values of 1 H r ; - and 13 C r , in particular, to identify the type of amino acid residue i. [0108] The present invention also relates to a method for sequentially assigning chemical shift values of aliphatic protons, 1 H a , aliphatic carbons, 13 C ah , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule. The method involves providing a protein sample and conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample including: (1) a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of the aliphatic protons of amino acid residue i-1, 1 H all ,. 1 , the aliphatic carbons of amino acid residue i-1, 13 C a ;-1 , the polypeptide backbone amide nitrogen of amino acid residue i, N,-, and the polypeptide backbone amide proton of amino acid residue i, 1H N ; and (2) a RD 3D HNNCAHA NMR experiment to measure and connect the chemical shift values of the α-proton of amino acid residue i, 'H" , the α-carbon of amino acid residue i, 13 C ; -, 15 N,-, and ! H N . Then, sequential assignments of the chemical shift values of 1H 3h , 13 C ah , 15 N, and 1H N are obtained by (i) matching the chemical shift values of the α- proton of amino acid residue i-1, 1H α / .ι and the α-carbon of amino acid residue i- 1, 13 C with the chemical shift values of 1 H α , and 13 C α ,-, (ii) using the chemical shift values of 1H ah / -ι and ^C 3 ' 1 ,. ! to identify the type of amino acid residue i-1 (Wϋthrich, NMR of Proteins and Nucleic Acids. Wiley, New York (1986); Grzesiek et al., J. Biomol. NMR. 3: 185-204 (1993), which are hereby incoφorated by reference in their entirety), and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using the chemical shift values to locate secondary structure elements within the polypeptide chain (Spera et al., J. Am. Chem. Soc. 113:5490-5492 (1991); Wishart et al., Biochemistry, 31:1647-1651, which are hereby incoφorated by reference in their entirety). [0109] In one embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D H α/β ,C α β ,CO,HA NMR experiment to measure and connect the chemical shift values of a β-proton of amino acid residue i, 1H β / , a β-carbon of amino acid residue i, 13 C β ,-, 1 H α ,-, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',. Then, sequential assignments of the chemical shift value of 13 C, are obtained by matching the chemical shift values of 1 H β ,-, 13 C β ,-, 1H α ,-, and 13 C α ,- measured by the RD 3D H α β ,C α β ,CO,HA NMR experiment with the sequentially assigned chemical shift values of 1H 13 , 13 C β , 1H α , 13 C α , 15 N, and 1H N measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment. [0110] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' ;-1 , 13 C α , 15 N,, and 1H N ,. Then, sequential assignments of the chemical shift value of 13 C',-.ι are obtained by matching the chemical shift value of 13 C α ; measured by the RD 3D HNN<CO.CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment. [0111] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to (i) a RD 3D H α β ,C α/β ,CO,HA NMR experiment to measure and connect the chemical shift values of a β-proton of amino acid residue i, 1 H β ,-, a β-carbon of amino acid residue i, 13 C β ,-, the α-proton of amino acid residue i, 1 H α , the α-carbon of amino acid residue i, 13 C" , and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',-, and (ii) a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of I3 C' ; , an α-carbon of amino acid residue i+1, 13 C α , + ι, a polypeptide backbone amide nitrogen of amino acid residue i+1, I5 N +! , and the polypeptide backbone amide proton of amino acid residue i+1, 1 H N , +1 . Then, sequential assignments are obtained by matching the chemical shift value of 13 C',- measured by the RD 3D HNN<CO.CA> NMR experiment with the chemical shift value of 13 C',- measured by the RD 3D H^C^CO^A NMR experiment. [0112] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D H α/β C α/β (CO)NHN NMR experiment (i) to measure and connect the chemical shift values of the α- and β-protons of amino acid residue i-1, H ' H, the α- and β- carbons of amino acid residue i-1, ^C^-i, 15 N,-, and 'H 1 " 1 ,-, and (ii) to distinguish NMR signals for the chemical shift values of 1H β M , 13 C β ;-1 , 1H α , and 13 C α M measured by the RD 3D H α/β C α/β (CO)NHN NMR experiment from NMR signals for the chemical shift values of 1 H ali /-1 and "c i other than 1 H α p and "C^M measured by the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment. [0113] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D H α/β ,C α/β ,N,HN NMR experiment to measure and connect the chemical shift values of 1H β , 13 C β , 1 H α , 13 C α ,, 15 N,-, and 'H 1 ^. Then, sequential assignments are obtained by matching the chemical shift values of 1H β ;, 13 C β ,-, 1H and 13 C ; measured by said RD 3D H α/β ,C α β ,N,HN NMR experiment with the chemical shift values of 1H 13 ,. ! , 13 C β , 1H α M , and 13 C α M measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0114] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to measure and connect the chemical shift values of I3 C β ,-, 13 C α / , 15 N,, and 1H N . Then, sequential assignments are obtained by matching the chemical shift values of 13 C β ,- and 13 C α ,- measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β M and 13 C α (-1 measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0115] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 2D HB.CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 1H β i, 13 C β ,-, and a δ-proton of amino acid residue i with an aromatic side chain, H ,. Then, sequential assignments are obtained by matching the chemical shift values of 1 H β / and 13 C β ,- measured by said RD 2D HB,CB,(CG,CD),HD NMR experiment with the chemical shift values of ! H β and 13 C β measured by the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, using the chemical shift values to identify amino acid residue i as having an aromatic side chain, and mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and by locating amino acid residues with aromatic side chains along the polypeptide chain. [0116] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, be further subjected to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, 1H 31 ' / , and aliphatic carbons of amino acid residue i, 13 C ah ,. Then, sequential assignments of the chemical shift values of 1H all j and 13 C ah ,-, the chemical shift values of a γ-proton, 1H γ , and a γ-carbon, 13 C γ ,-, in particular, are obtained by (i) matching the chemical shift values of 1H ah and 13 C ah measured using the RD 3D H,C,C,H-COS Y NMR experiment or the RD 3D H,C,C,H-TOCS Y NMR experiment with the chemical shift values of 'H 13 ;, 13 C β ,-, 1H α , and 13 C α ; measured by the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment and the RD 3D HNNCAHA NMR experiment, and (ii) using the chemical shift values of 1H a1 ' and 13 C aIl j, the chemical shift values of 'if 7 ; and 13 C Y , in particular, to identify the type of amino acid residue i. [0117] Another aspect of the present invention involves a method for obtaining nearly complete assignments of chemical shift values of ! H, 13 C and 15 N of a protein molecule (excluding only chemical shift values of 13 C δ and 15 N ε2 of glutamines, of 13 C γ and 15 N δ2 of asparagines, of 13 C ε3 , 1H ε3 , 13 C ζ2 , 1H ζ2 , 13 C ζ3 , 1H ζ3 , 13 C η2 , and 1H η2 groups of tryptophans, of 13 C ε and 1H ε of methionines, and of labile sidechain protons that exchange rapidly with the protons of the solvent water) (Yamazaki et al., J. Am. Chem. Soc. 115:11054-11055 (1993), which is hereby incoφorated by reference in its entirety), which are required for the determination of the tertiary structure of a protein in solution (Wuthrich, NMR of Proteins and Nucleic Acids. Wiley, New York (1986), which is hereby incoφorated by reference in its entirety). The method involves providing a protein sample and conducting four reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample, where (1) a first experiment is selected from the group consisting of a RD three-dimensional (3D) H α/β C α/β (CO)NHN NMR experiment, a RD 3D HA,CA,(CO),N,HN NMR experiment, and a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment for obtaining sequential correlations of chemical shift values; (2) a second experiment is selected from the group consisting of a RD 3D HNNCAHA NMR experiment, a RD 3D H α β ,C α/β ,N,HN NMR experiment, and a RD 3D HNN<CO,CA> NMR experiment for obtaining intraresidue correlations of chemical shift values; (3) a third experiment is a RD 3D H,C,C,H-COSY NMR experiment for obtaining assignments of aliphatic and aromatic sidechain chemical shift values; and (4) a fourth experiment is a RD 2D HB,CB,(CG,CD),HD NMR experiment for obtaining assignments of aromatic sidechain chemical shift values. [0118] In one embodiment of this method, the protein sample could be further subjected to a RD 2D H,C,H-COSY NMR experiment for obtaining assignments of aliphatic and aromatic sidechain chemical shift values. [0119] In another embodiment of this method, the first experiment is the RD 3D H α β C tx/β (CO)NHN NMR experiment and the second experiment is the RD 3D HNNCAHA NMR experiment. [0120] In another embodiment, the protein sample could, in addition to the RD 3D H α β C α β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HA,CA,(CO),N,HN NMR experiment to distinguish between NMR signals for 1 H 13 C α and 1H β / 13 C β from the RD 3D H α β C α/β (CO)NHN NMR experiment. [0121] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,(C- TOCSY-CO),N,HN NMR experiment to obtain assignments of chemical shift values of 1 H ali and 13 C 3li . [0122] In another embodiment, the protein sample could, in addition to the RD 3D H α β C α β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D NMR experiment to obtain assignments of chemical shift values of 1H β and 13 C β . [0123] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment to obtain assignments of chemical shift values 1 ^ of polypeptide backbone carbonyl carbons, C ' . [0124] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H^P J C^ J CO J HA NMR experiment to obtain assignments of chemical shift values 1 " of polypeptide backbone carbonyl carbons, C\ [0125] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment and a RD 3D H α/β ,C α β ,CO,HA NMR experiment to obtain assignments of chemical shift values of 13 C. [0126] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values 1 ι of H and C of aliphatic sidechains. [0127] In another embodiment, the protein sample could, in addition to the RD 3D H α/p C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values 1 1 -3 of H and C of aromatic sidechains. [0128] In another embodiment, the protein sample could, in addition to the RD 3D H α/β C α/β (CO)NHN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . [0129] In yet another embodiment of this method, the first experiment is the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the second experiment is the RD 3D HNNCAHA NMR experiment. [0130] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HA,CA,(CO),N,HN NMR experiment to identify NMR signals for 1H α / 13 C α in the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0131] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H^ β ,C^ p ,N,HN NMR experiment to obtain assignments of chemical shift values of ^ and 13 ^. [0132] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, C. [0133] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H α β ,C α/β ,CO,HA NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, C. [0134] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COS Y NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment and a RD 3D H α/β ,C α β ,CO,HA NMR experiment to obtain assignments of chemical shift values of C . [0135] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aliphatic sidechains. [0136] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HNNMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCS Y NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aromatic sidechains. [0137] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, RD 3D H,C,C,H-COSY.NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . [0138] In yet another embodiment of this method, the first experiment is the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the second experiment is the RD 3D H α β ,C α β ,N,HN NMR experiment. [0139] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α/β ,C α/β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HA,CA,(CO),N,HN NMR experiment to identify NMR signals for 'H* and 13 C α in the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0140] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α/β ,C α β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H α/β C α β (CO)NHN NMR experiment to identify NMR signals for 1 H α β and 13 C α β in the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment. [0141] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α/β ,C α/β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HNN<CO.CA> NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, C ' . [0142] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α β ,C α/β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subj ected to a RD 3D H α β ,C α β ,CO,HA NMR experiment to obtain assignments of chemical shift values 1 of polypeptide backbone carbonyl carbons, C ' . [0143] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α β ,C α β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HNN<CO,CA> NMR experiment and a RD 3D H α β ,C α/β ,CO,HA NMR experiment to obtain assignments of chemical shift values of 13 C. [0144] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α/β ,C α/β ,N,HN NMR experiment, RD 3D H,C,C,H-COS Y NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values i n of H and C of aliphatic sidechains. [0145] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H α/β ,C α β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values 1 1 ^ of H and C of aromatic sidechains. [0146] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D H <x β ,C ot β ,N,HN NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . [0147] In yet another embodiment of this method, the first experiment is the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the second experiment is the RD 3D HNN<CO,CA> NMR experiment. [0148] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNN<CO.CA> NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D HA,CA,(CO),N,HN NMR experiment to identify NMR signals for 1 H α and 13 C α in the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. [0149] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment, RD 3D HNN<CO,CA> NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H α/β C α/β (CO)NHN NMR experiment to identify NMR signals for 1 H α β and 13 C α/β in the RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment. [0150] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNN<CO,CA> NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D jj α/β Q θt/β Q JJ^ NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, C ' . [0151] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNN<CO,CA> NMR experiment, RD 3D H,C,C,H-COS Y NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aliphatic sidechains. [0152] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNN<CO,CA> NMR experiment, RD 3D H,C,C,H-COSY NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a RD 3D H,C,C,H-TOCS Y NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aromatic sidechains. [0153] In another embodiment, the protein sample could, in addition to the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, RD 3D HNN<CO.CA> NMR experiment, RD 3D H,C,C,H-COS Y NMR experiment, and RD 2D HB,CB,(CG,CD),HD NMR experiment, be further subjected to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C P . [0154] In addition, the above-described method for obtaining assignments of chemical shift values of 1H, I3 C and 15 N of a protein molecule can involve further subjecting the protein sample to nuclear Overhauser effect spectroscopy (NOESY) (Wϋthrich, NMR of Proteins and Nucleic Acids. Wiley, New York (1986), which is hereby incoφorated by reference in its entirety), to NMR experiments that measure scalar coupling constants (Eberstadt et al., Angew. Chem. Int. Ed. Engl.. 34:1671-1695 (1995); Cordier et al., J. Am. Chem. Soc. 121:1601-1602 (1999), which are hereby incoφorated by reference in their entirety), or to NMR experiments that measure residual dipolar coupling constants (Prestegard, Nature Struct. Biol.. 5:517-522 (1998); Tjandra et al., Science. 278:1111-1114 (1997), which are hereby incoφorated by reference in their entirety), to deduce the tertiary fold or tertiary structure of the protein molecule. [0155] A standard set of nine experiments (labeled with asterisks in Table 2) can be employed for obtaining nearly complete resonance assignments of proteins including aliphatic and aromatic side chain spin systems. Table 2. NMR experiments acquired 2 for the 8.5 kDa protein "Z-domain" Experiment Indirect b Complex Measurement Minimal 0 dimension(s) points [ms] time [h] measurement time [h] with/without central peak 3D spectra for sequential backbone connectivities: **H αp C α/p (CO)NHN α> 1 ( lϊ C a/p ) 6.3; 95 9.2 4.6/2.3 ω 2 ( 15 N) 21.5; 28 HACAtCCNHN ω,( 13 C α ) 6.5; 54 5.4/2.7 d 5.4/2.7 ω 2 ( 15 N) 21.5; 28 HC(C-TOCSY-CO)NHN d ω 1 ( ,3 C βp ) 6.1; 90 17.9 4.5/2.3 ω 2 ( 15 N) 21.5; 28 3D spectra for intraresidual backbone connectivities: **HNNCAHA ω,( 13 C α ) 6.6; 51 5.0 2.5 /n.a. ω 2 ( 15 N) 21.5; 28 *jjα/β £ α/β COHA <D 1 ( ,3 C BP ) 6.3; 95 10.0 5.0/2.5 ω 2 ( 13 C=0) 17.8; 32 if^C^NHN ω 1 ( ,3 C α/p ) 6.0; 90 17.1 4.3 / 2.2 ω 2 ( 15 N) 21.5; 28 *HNNCACB ω,( 13 C αβ ) 6.6; 56 8.0 n.a./ 2.0 ω 2 ( 15 N) 21.5; 28 3D spectrum for intra- and sequential backbone connectivities: *HNN<CO.CA> ω,( 13 C=0) 8.0/16.0 e ;54 5.5 2.8 /n.a. ω 2 (> 5 N ) 21.5; 28 3D spectra for assignment of aliphatic resonances: **HCCH-COSY e> i ("C) 6.3; 95 6.2 3.1/1.6 <D 2 (»C) 6.4; 20 **HCCH-TOCSY f ωι ( 13 C) 6.3; 95 7.0 3.5/1.7 ω 2 ( 13 C) 6.4; 20 2D spectra for assignment of aromatic resonances: **HBCB(CGCD)HD ωι ( 13 Q 6.3; 95 5.3 0.1 / 0.05 * * 'H-TOCSY-HCH-COSY f ω,( 13 C) 15; 150 3.4 0.2 / n.a a 1 mM solution of "Z-domain" of Staphylococcal protein A 25 at T= 25 °C. The Η carrier for 'H- frequency labeling in the projected "HC"-dimensions was set to 0 ppm relative to DSS. t max denotes the maximal evolution time. Spectra forming a "standard set" that has been inferred from the present study (see text) are labeled with an asterisk (* or **), and those spectra which can be designated a "minimal" set are labeled with a double-asterisk (**). b Direct dimension: t max = 73 ms / 512 complex points. c The minimal measurement time (rounded) was calculated for the acquisition of a single transient per FID, either with (left number) or without (right number) acquisition of central peaks. Other spectral parameters were assumed to be unchanged. Note that central peak acquisition (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996), which is hereby incorporated by reference in its entirety) from I3 C magnetization requires recording of two data sets that are added and subtracted to generate subspectra I and II. d The mixing times for the 13 C-TOCSY relay was set to 14 ms or 21 ms. e The increment for 13 C α chemical shift evolution was scaled (Szyperski et al., J. Am. Chem. Soc. 115:9307-9308 (1993); Szyperski et al., J. Magn. Reson.. B 108, 197-203 (1995), which are hereby incoφorated by reference in their entirety) by a factor of 0.5 relative to the I3 C=0 evolution. f The mixing time for the ] H-TOCSY relay was set to 25 ms. [0156] For larger proteins, complementary recording of highly sensitive 3D HACA(CO)NHN promises (i) to yield spin systems which escape detection in H α/β C ct/β (CO)NHN, and (ii) to offer the distinction of α- and β-moiety resonances by comparison with H α β C tx/β (CO)NHN. Furthermore, employment of 50% random fractional protein deuteration (LeMaster, Annu. Rev. Biophvs. Biophys. Chem.. 19:43-266 (1990); Nietlispach et al., J. Am. Chem. Soc. 118:407-415 (1996); Shan et al., J. Am. Chem. Soc. 118:6570-6579 (1996); Leiting et al., Anal. Biochem.. 265:351-355 (1998); Hochuli et al., J. Biomol. NMR. 17:33-42 (2000), which are hereby incoφorated by reference in their entirety) in combination with the standard suite of NMR experiments (or transverse relaxation-optimized spectroscopy (TROSY) versions thereof) is attractive. The impact of deuteration for recording 4D H α/β C α/β (CO)NHN for proteins reorienting with correlation times up to around 20 ns (corresponding to a molecular weight around 30 kDa at ambient T) has been demonstrated (Nietlispach et al., J. Am. Chem. Soc. 118:407-415 (1996) , which is hereby incoφorated by reference in its entirety). Accordingly, 3D H tx/β C α β (CO)NHN can be expected to maintain its pivotal role for obtaining complete resonance assignments (Figure 4) for deuterated proteins at least up to about that size. Furthermore, protein deuteration offers the advantage that HNNCACB, which can be expected to become significantly less sensitive than HNNCAHA for larger non-deuterated systems, (Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which is hereby incoφorated by reference in its entirety) can be kept to recruit 13 C β chemical shifts for sequential assignment (Shan et al., J. Am. Chem. Soc. 118:6570-6579 (1996), which is hereby incoφorated by reference in its entirety). [0157] If solely chemical shifts are considered, the unambiguous identification of peaks pairs is more involved whenever multiple peak pairs with degenerate chemical shifts in the other dimensions are present. The acquisition of the corresponding central peaks addresses this complication in a conceptually straightforward fashion. However, it is important to note that pairs of peaks generated by a chemical shift in-phase splitting have quite similar intensity. In contrast, peak pairs arising from different moieties, possible located in different amino acid residues, most often do not show similar intensity. This is because the nuclear spin relaxation times, which determine the peak intensities, vary within each residue as well as along the polypeptide chain. One may thus speak of a "nuclear spin relaxation time labeling" of peak pairs, which makes their identification an obvious task in most cases. [0158] Using cryogenic probes can reduce NMR measurement times by about a factor of 10 or more (Flynn et al., J. Am Chem. Soc. 122:4823-4824 (2000), which is hereby incoφorated by reference in its entirety). Hence, the standard set of nine experiments (Table 2) could have been recorded with the same signal-to-noise ratios measured for the present study in about 6 hours using a cryogenic probe, i.e., the high sensitivity of cryogenic probes shifts even the recording of RD NMR experiments entirely into the sampling limited data acquisition regime. In view of this dramatic reduction in spectrometer time demand, minimally achievable RD NMR measurement times are of keen interest (Table 2) to be able to adapt the NMR measurement times to sensitivity requirements in future HTP endeavours. [0159] If the standard set of experiments would have been recorded with a single transient per increment, 21.8 hours of spectrometer measurement time would have been required (Table 2). This is still about 3.5 times longer than the 6 hours alluded to above, which would be needed on a currently available cryogenic probe. To further reduce the measurement time, and in view of the aforementioned 'spin relaxation time labeling' of peak pairs', one may then decide to also discard the use of 13 C-steady state magnetization for central peak detection. This would lead to a diminished requirement of 15.5 hours for the standard, or 8.1 hours for the minimal set of experiments (four projected 4D and two projected 3D spectra; Table 2). Hence, the measurement time of the minimal set of RD NMR experiments (which provides complete resonance assignments for Z-domain) could actually be neatly adjusted to the sensitivity requirements of a cryogenic probe. [0160] Although RD NMR was proposed in 1993 (Szyperski et al., J. Biomol. NMR. 3:127-132 (1993); Szyperski et al., J. Am. Chem. Soc. 115:9307-9308 (1993), which are hereby incoφorated by reference in their entirety), its wide-spread use has been delayed by the more demanding spectral analysis when compared to conventional TR NMR. In particular, the necessity to extract chemical shifts from in-phase splittings suggests that strong computer support is key for employment of RD NMR on a routine basis. This can be readily addressed by using automated resonance assignment software for automated analysis of RD TR NMR data. [0161] In conclusion, the joint employment of RD NMR spectroscopy, cryogenic probes, and automated backbone resonance assignment will allow one to determine a protein's backbone resonance assignments and secondary structure in a short time. EXAMPLES [0162] The following examples are provided to illustrate embodiments of the present invention but are by no means intended to limit its scope. Example 1 - Sample Preparation [0163] NMR measurements were performed using a 1 mM solution of uniformly 13 C/ 15 N emiched "Z-domain" of the Staphylococcal protein A (Tashiro et al., J. Mol. Biol. 272:573-590 (1997); Lyons et al., Biochemistry. 32:7839-7845 (1993), which are hereby incoφorated by reference in their entirety) dissolved in 90% D 2 O/10% H 2 O (20 mM K-PO 4 ) at pH = 6.5. Example 2 - NMR Spectroscopy [0164] Multidimensional NMR experiments (Figure 1 ; Table 1) were recorded for a 1 mM solution of the 8.5 kDa protein "Z-domain" at a temperature of 25 °C. The spectra (Table 2) were assigned, and the chemical shifts obtained from RD NMR (Table 3) were in very good agreement with those previously determined at 30 °C using conventional triple resonance (TR) NMR spectroscopy (Tashiro et al., J. Mol. Biol. 272:573-590 (1997); Lyons et al., Biochemistry. 32:7839-7845 (1993), which are hereby incoφorated by reference in their entirety). Table 3: Chemical shifts of the Z-domain (in ppm relative to DSS) determined at T = 25 °C Table 3 (continued) Table 3 (continued) [0165] NMR experiments were recorded at a temperature of 25°C on a Varian Inova 600 spectrometer equipped with a new generation 1H{ 13 C, 15 N} triple resonance probe which exhibits a signal-to-noise ratio of 1200:1 for a standard 0.1% ethylbenzene sample. At 25 °C, the correlation time for the overall rotational reorientation of the Z-domain was 4.5 ns (as inferred from measurements of T \P IT \ polypeptide backbone 15 N spin relaxation time ratios (Kay et al., Biochemistry, 28:8972-8979 (1989); Szyperski et al., J. Biomol. NMR. 3:151-164 (1993), which are hereby incoφorated by reference in its entirety)). This value was well within the 3-10 ns range usually encountered for medium- sized proteins at ambient temperatures. Hence, the, results obtained in the framework of the present study were representative for medium-sized systems in the molecular weight range from about 5 to 20 kDa. NMR spectra were processed and analyzed using the programs PROSA (Gϋntert et al., J. Biomol. NMR, 2:619- 629 (1992), which is hereby incoφorated by reference in its entirety) and XEASY (Bartels et al., J. Biomol. NMR. 6:1-10 (1995), which is hereby incoφorated by reference in its entirety), respectively. [0166] Specific embodiments of the 8 new RD NMR experiments disclosed by the present invention as well as 3 other RD NMR experiments that have previously been published, were implemented for the present study. Figure 1 provides a survey of (i) the names, (ii) the magnetization transfer pathways and (iii) the peak patterns observed in the projected dimension of each of the 8 RD NMR experiments disclosed by the present invention as well as 3 other RD NMR experiments that have previously been published. The group comprising the first three experiments are designed to yield "sequential" connectivities via one-bond scalar couplings: 3D H α β C α β (CO)NHN (Figure 1 A; Szyperski et al., J. Magn. Reson., B 105: 188-191 (1994), which is hereby incoφorated by reference in its entirety), 3D HACA(CO)NHN (Figure IB), and 3D HC(C-TOCSY-CO)NHN (Figure IC). The following three experiments provide "intraresidual" connectivities via one-bond scalar couplings: 3D HNNCAHA (Figure ID; Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which is hereby incoφorated by reference in its entirety), 3D H α/β C α/β COHA (Figure IE), and 3D H^ β C α/β NHN (Figure IF). 3D HNN<CO,CA> (Figure IG; Szyperski et al., Magn. Reson.. B 108: 197-203 (1995); Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996), which are hereby incoφorated by reference in their entirety) offers both intraresidual 1H N - 13 C α and sequential 1H N - 13 C connectivities. Although 3D HNNCAHA (Figure ID), 3D If /p C α p NHN (Figure IF) and 3D HNN<CO,CA> (Figure IG) also provide sequential connectivities via two-bond 13 C α ;„ι- 15 N,- scalar couplings, those are usually smaller than the one- bond couplings (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety), and obtaining complete backbone resonance assignments critically depends on experiments designed to provide sequential connectivities via one-bond couplings (Figures 1D-F). 3D HCCH-COSY (Figure IH) and 3D HCCH-TOCSY (Figure II) allow one to obtain assignments for the "aliphatic" side chain spin systems, while 2D HBCB(CDCG)HD (Figure 1 J) and 2D 1H-TOCSY-relayed HCH-COSY (Figure IK) provide the corresponding information for the "aromatic" spin systems. [0167] The RD NMR experiments are grouped accordingly in Table 1, which lists for each experiment (i) the nuclei for which the chemical shifts are measured, (ii) if and how the central peaks are acquired and (iii) additional notable technical features. State-of-the art implementations (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996); Kay, J. Am. Chem. Soc. 115:2055-2057 (1993); Grzesiek et al., J. Magn. Reson.. 99:201-207 (1992); Montelione et al, J. Am. Chem. Soc. 114:10974-10975 (1992); Boucher et al., J. Biomol. NMR. 2:631-637 (1992); Yamazaki et al., J. Am. Chem. Soc. 115:11054-11055 (1993); Zerbe et al., J. Biomol. NMR. 7:99-106 (1996); Grzesiek et al., J. Biomol. NMR. 3:185-204 (1993), which are hereby incoφorated by reference in their entirety) making use of pulsed field z-gradients for coherence selection and/or rejection, and sensitivity enhancement (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety) were chosen, which allow executing these experiments with a single transient per acquired free induction decay (FID). Semi (Grzesiek et al., J. Biomol. NMR. 3:185-204 (1993), which is hereby incoφorated by reference in its entirety) constant-time (Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996), which is hereby incoφorated by reference in its entirety) chemical shift frequency-labeling modules were used throughout in the indirect dimensions in order to minimize losses arising from transverse nuclear spin relaxation. Figures 2A-2K provide comprehensive descriptions of the RD NMR r.f. pulse sequences including eight previously unpublished RD NMR r.f. pulse schemes. [0168] The maximal chemical shift evolution times, which largely determine the spectral resolution, as well as the measurement times invested for the present study (between 2.7 and 17.1 hours per spectrum) are given in Table 2. The S/N ratio achieved per unit of measurement time, i.e., the sensitivity, shows only little dependence on the relaxation delay between scans, T de , provided that 0.7 ' T \ < J e i < 1.5 ' T \ (Abragam, Principles of Nuclear Magnetism., Clarendon Press:Oxford (1986); Ernst et al., Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press:Oxford (1987), which are hereby incoφorated by reference in their entirety). Hence, T κ \ was set to rather short values around 0.7 seconds. Furthermore, to ensure efficient comparison of peak patterns and shapes manifested along the projected dimension in the various i n spectra, the RD NMR experiments in which H and C are jointly observed in the projected dimension ("HC"-type experiments; Figure 1) were acquired with virtually the same maximal evolution time in t\( C). [0169] In total, fourteen RD TR NMR experiments were recorded: 3D HC(C-TOCSY-CO)NHN and 3D HCCH-TOCSY were acquired with two different mixing times (14 ms and 21 ms) each, and 3D HNNCAHA were acquired with and without adiabatic decoupling of 13 C β resonances for comparison (Kupce et al., J. Magn. Reson., A 115:273-277 (1995); Matsuo et al., J. Magn. Reson. B 113:190-194 (1996), which are hereby incoφorated by reference in their entirety). Except for 3D HNNCAHA. 3D HNN<CO,CA> and 2D 1H- TOCSY-relayed HCH-COSY (Figure 1), central peaks were derived from 13 C magnetization (Figure 1; Table 1). Hence, two subspectra, I and II containing the peak pairs and central peaks respectively, were generated (Szyperski et al., J. Am. Chem. Soc. 118:8146-8147 (1996); Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which are hereby incoφorated by reference in their entirety) for eight of the RD NMR experiments (Figure 1). Overall, twenty-four processed RD NMR (sub)spectra were thus obtained for a detailed exploration of relative sensitivities and data collection strategies. These were complemented with conventional 3D HNNCACB data (Table 2; Wittekind et al., J. Magn. Reson.. B 101:201-205 (1993), which is hereby incoφorated by reference in its entirety). Example 3 - Adjustment of r.f. Carrier Frequencies to Minimize Spectral Overlap [0170] In view of potential peak overlap in spectra recorded for larger proteins, it is of central importance to properly set the r.f. carrier frequencies. An illustrative example is the 3D HNNCAHA experiment, where adjustments of the carrier frequencies allows one to place central peaks and upfϊeld and downfield component of the peak pairs into three separated spectral regions (Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which is hereby incoφorated by reference in its entirety). This is accomplished by choosing a 1H-carrier frequency that yields a minimal in-phase splitting exceeding the 13 C α chemical shift dispersion (Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which is hereby incoφorated by reference in its entirety). As a consequence, the generation of peak pairs does not lead to increased spectral overlap. In fact, the increase in the number of peaks expected for 3D HNNCAHA relative to 3D HNNCA was comparable to the increase observed in widely used conventional 3D HNNCACB. 3D HNNCACB exhibited up to four peaks for each amino acid residue: (Wittekind et al., J. Magn. Reson.. B 101 :201-205 (1993), which is hereby incoφorated by reference in its entirety) an intraresidue and a sequential connectivity in each of the quite well separated spectral regions containing the 13 C α and 13 C β resonances, respectively. Similarly, 3D HNNCAHA comprised the three separated regions each of which may exhibit one intraresidual and one sequential connectivity per amino acid residue (Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which is hereby incoφorated by reference in its entirety). Example 4 - Sensitivity Analysis of RD NMR Experiments [0171] Since a reduction of dimensionality in a NMR experiment preserves the relative sensitivity of the higher-dimensional parent experiments, evaluating the relative sensitivity of an entire set of multidimensional NMR experiments designed to provide complete resonance assignment for a protein is of general interest. The relative sensitivity of the RD NMR and 3D HNNCACB experiments were analyzed first, by determining the yield of peak detection, i.e., the ratio of observed peaks over the total number of expected peaks, and second, by separately assessing the S/N ratio distributions of peaks belonging to either RD peak pairs or central peaks. Moreover, distinct S/N distributions were then generated according to (i) the atom position involved (e.g., α- or β-moiety in H α/β C α/β (CO)NHN), (ii) the involvement of intraresidue or sequential connectivities (e.g., 13 C α -W and 13 C α M -1H N ,- connectivities in H α β C α β NHN) and (iii) the classification of COSY-type, relay and double-relay peaks in HCCH TOCSY. In total, 127 S/N distributions were thus analyzed (Figure 5; Table 4). For 3D (Fig. IE), there were 4 distributions each: - and β-connectivities in subspectra I and II. For 3D HACA(CO)NHN (Fig. IB) and 2D HBCB(CDCG)HD (Fig. 1 J), there were 2 distributions each: connectivities in subspectra I and II. For 3D HC(C-TOCSY- CO NHN (Fig. IC) recorded with 14 and 21 ms mixing time, respectively, there were 10 distributions each: -, β-, γ-, δ- and ε-connectivities in subspectra I and II. For 3D HNNCAHA (Fig. ID), there were 8 distributions: intraresidual and sequential connectivities recorded with and without adiabatic 13 C β decoupling. For 3Z) H α β C α/β 7vΗiV(Fig. IF), there were 8 distributions: intraresidual and sequential α- and β-connectivities in subspectra I and II. For 3D HNNCACB, there were 4 distributions: intraresidual and sequential - and β-connectivities. For 3D HNN<CO,CA> (Fig. IG), there were 2 distributions: peak pairs and central peaks. For 3D HCCH-COSY ' (Fig. 1Η), there were 10 distributions: connectivities detected on α-, β-, γ-, δ- and ε-protons for subspectra I and II. For 3D HCCH-TOCSY (Fig. 1 Η) recorded with 14 and 21 ms mixing time, there were 30 distributions each: COSY-type, relay and double-relay connectivities detected on α-, β-, γ-, δ- and ε-protons for subspectra I and II. For 2D ' H-TOCSY-relayed HCH-COSY (Fig. IK), there were 3 distributions for connectivities detected on δ-, ε- and ζ-protons. In order to exclude a bias arising from longer transverse relaxation times in several highly disordered terminal residues (Tashiro et al., Mol. Biol.. 272:573-590 (1997); Lyons et al., Biochemistry. 32:7839-7845 (1993), which are hereby incoφorated by reference in their entirety), the N- terminal octapeptide segment comprising residues "-13" to "-6" (in the numbering chosen in Tashiro et al., J. Mol. Biol., 272:573-590 (1997) and Lyons et al., Biochemistry, 32:7839-7845 (1993), which are hereby incoφorated by reference in their entirety) was not considered for the current sensitivity analyses. To rank the NMR experiments (Table 2) according to relative sensitivity, focus was put on (i) the peak detection yield and (ii) the averaged S/N ratios of those peak categories encoding the prime information to be obtained from a given spectrum, i.e., wtraresidual connectivities in HNNCAHA (Figure ID), Ff^C^COHA (Figure 1 E), H α p C α/p NHN (Figure 1 F) and HNNCACB, correlation peaks in HCCH-COSY and relay connectivities in HCCH TOCSY. For comparison, these averaged S/N ratios were subsequently divided by the square-root of the NMR measurement time (Tables 2 and 4) and scaled relative to the most sensitive experiment, i.e., HACA(CO)NHN (Table 4; Figure 5). Table 4: Signal-to-noise analysis of RD NMR spectra recorded for the Z-domain; sub I 60/60(100%) E6.41+10.70 60/60(100%) E2.29+14.31 all 120/120(100%)* 04.35 8.03 / 0.56 * Table 4 (continued) Table 4 (continued) Table 4 (continued) Table 4 (continued) a / and z'-l denote two sequentially located amino acid residues. The first column provides (i) the name of the RD NMR experiment (in bold), (ii) the type of subspectrum (sub I and sub II corresponding to the subspectra containing peak pairs and central peaks, respectively), and, (iii) for the TOCSY experiments the mixing time (2cyc = 14 ms; 3cyc = 21 ms) and the type of peak (COSY-peaks, relay peaks and double relay peak). The second column indicates the atom position involved ("type" of correlation), the third column provides the detection yield (see text and the legend of Figure 5), and the fourth column contains the average S/N ratio and the corresponding standard deviation for all cases where the detection yield (third column) was high. The right-most column affords the average S/N ratio divided by the square root of the measurement time (Table 2), i.e., the sensitivity. The sensitivity scaled relative to HACA(CO)NHN (number on the right) is also given. Rows labeled with an asterisk (*) contain the values used to create Figure 5. [0172] In principle, the relative sensitivities of NMR experiments can be estimated by calculating transfer amplitudes (Szyperski et al., J. Biomol. NMR, 11 :387-405 (1998); Ernst et al., Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press:Oxford (1987); Wittekind et al., J. Magn. Reson.. B 101:201-205 (1993); Buchler et al., J. Magn. Reson.. 125:34-42 (1997), which are hereby incorporated by reference in their entirety). However, these calculations rely on various assumptions such as knowledge about nuclear spin relaxation times, or neglect of Brinhomogeneity and imperfections of composite pulse decoupling sequences. Hence, an experimental approach is mandatory to obtain a thorough sensitivity assessment, in particular for the experiments employed for side chain resonance assignments. [0173] The key yields of peak detection as well as the relative sensitivity of the NMR spectra recorded for the present study (Tables 1 and 2) are shown in Figure 5. The S/N distribution analysis that was required to generate Figure 5 is provided in Table 4. Since adiabatic 13 C β decoupling (Kupce et al., J. Magn. Reson.. A 115:273-277 (1995); Matsuo et al, J. Magn. Reson. B 113:190-194(1996), which are hereby incorporated by reference in their entirety) increased the sensitivity of 3D HNNCAHA by a factor of about 1.5 (Figure 5; Table 4), only the decoupled spectrum was considered in this analysis. Among the group of experiments designed to yield sequential connectivities (Figure 4), all of the expected peaks were detected for 3D HACA(CO)NHN (Figures IB and 4) and 3D H α/(3 C α/β (CO)NHN (Figures 1 A and 4). In spite of the rather long measurement time of 17 hours (Table 2), a substantial fraction of the expected cross peaks was not observed for 3D HC(C-TOCS Y-CO)NHN (Figures 1 C and 4). Evidently, losses due to rotating frame transverse relaxation and off-resonance effects during the C-C TOCSY relay are significantly larger than those encountered when implementing the C-C COSY step which expands 3D HACA(CO)NHN to 3D H α/β C α/β (CO)NHN. Moreover, due to the oscillatory nature of the spin modes associated with total correlation, (Ernst et al., Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press:Oxford (1987), which is hereby incorporated by reference in its entirety) the average S/N ratio observed for a given atom position critically depends on the particular choice of the mixing time in 3D HC(C-TOCSY-CO)NHN (Table 4): e.g., several β-moiety signals are lost at the expense of detecting additional γ-, δ- or ε-moiety cross peaks for the long aliphatic side chains when increasing the mixing time from 14 ms to 21 ms (Figure 4). [0174] Among the experiments providing traresidue connectivities (Figure 6), HNNCAHA (Figures ID and 6 A) exhibited complete detection of expected peaks and a sensitivity which is comparable to H α β C /β (CO)NHN, but significantly higher than H^C^COHA (Figures IE and 6B) and H α β C α/β NHN (Figures IF and 6C). The latter experiment, designed in an 'out-and-stay fashion' as CBCANHN (Kay, J. Am. Chem. Soc. 115:2055-2057 (1993), which is hereby incorporated by reference in its entirety), is the least sensitive among the suite of RD NMR experiments studied here and can thus be expected to be primarily of use for smaller proteins. However, virtually all expected correlations were observed. Conventional HNNCACB is slightly more sensitive than HNNCAHA and equally sensitive as H α β C α/β (CO)NHN. However, when considering symmetrization of [α>ι( C),ω 3 (1H N )]-strips about central peaks along ω l5 (Szyperski et al., J. Magn. Reson.. B 108: 197-203 (1995); Szyperski et al., I Biomol. NMR. 11 :387-405 (1998), which are hereby incoφorated by reference in their entirety) HNNCAHA can be considered to be more sensitive than HNNCACB even for smaller proteins. HNN<CO.CA> (Figure IG) offers both intraresidue 1 H N - 13 C α (peak pairs) and sequential 1H N - 13 C (central peaks) connectivities. In accordance with the outstanding sensitivity of HNNCO, central peak detection in HNN<CO.CA> was by far the most sensitive observed in all spectra, while the sensitivity of corresponding peak pair detection was comparable to HNNCAHA. Hence, central peaks in 3D HNN<CO,CA> may be recruited for secure spin system identification (Zimmerman et al., J. Mol. Biol., 269:592-610 (1997), which is hereby incorporated by reference in its entirety) in cases of overlap in 2D [^N^Hj-HSQC. [0175] The sensitivity of peak pair detection in 3D HCCH COSY, required for aliphatic side chain assignment, was again comparable to 3D HNNCAHA. while detection of relayed COSY peaks in 3D HCCH TOCSY was slightly less sensitive. The incompleteness of relay peak detection was, however, to some extent due to signal overlap (Table 4). 2D HBCB(CDCG)HD and 2D 1H- TOCSY-relayed HCH-COSY. providing the aromatic spin system assignments, appeared to be rather sensitive. However, analysis for the Z-domain was biased by (i) the relatively small number of aromatic residues, and (ii) their partly flexibly disordered nature (His(-4), Phe 5 and Phe 13 exhibit local displacements that are well above the average for residues buried in the molecular core; protein data bank accession code: 2SPZ). When involving only those aromatic rings that are apparently not flexibly disordered, 2D HBCB(CDCG)HD appeared to be slightly less sensitive than 3D HCCH COSY. [0176] Overall (Figure 5), (i) outstanding sensitivity was found for 3D HACA(CO)NHN, (ii) similar sensitivity was found for 3D H α β C tx β (CO)NHN, 3D HNNCAHA. 3D HNN<CO,CA>, 3D HNNCACB, 3D HCCH COSY and 2D 1H- TOCS Y-relayed HCH-COSY. (iii) slightly reduced sensitivity was found for 3D H^C^COHA, 2D HBCB(CDCG)HD and relay peak detection in 3D HCCH TOCSY, and (iv) the lowest sensitivity was found for 3D HC(C-TOCSY- CO)NHN and 3D ϊf^C o p NHN. In the "H^ β C α β -experiments, the averaged intensity of the α- and β-moiety peak pairs was quite similar (though the S/N distribution of the β-peaks was broader reflecting larger variations in transverse relaxation times), and the central peaks exhibited a sensitivity of about two thirds relative to the individual peaks of the peak pairs. However, since the non- selective C ^-relaxation times are shorter than the H .T ϊ -times at higher molecular weight (Abragam, Principles of Nuclear Magnetism.. Clarendon Press:Oxford (1986); Ernst et al., Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press:Oxford (1987), which are hereby incorporated by reference in their entirety), the relative sensitivity of central peak detection using 13 C-magnetization becomes more favorable for larger systems. Moreover, the relative sensitivity of the various experiments shifts relative to each other with increasing molecular weight (Buchler et al., J. Magn. Reson.. 125:34-42 (1997), which is hereby incorporated by reference in its entirety). In particular, 3D HNNCACB and 3D H α/β C α/β COHA can be expected to loose relative sensitivity for larger systems since transverse magnetization resides comparably long on rapidly relaxing 13 C α . Example 5 - HTP Assignment Strategy: A "Standard Set" of RD NMR Experiments [0177] The comprehensive analysis of the suite of multidimensional spectra recorded for the present study (Figure 5; Tables 1 and 2) lays the foundation to devise strategies for RD NMR-based HTP resonance assignment of proteins. [0178] For proteins in the molecular weight range up to about 20 kDa, 3D H α/β C /β (CO)NHN plays a pivotal role (Figure 7). Firstly, the peak patterns observed along <o \ ( 13 C a ) in subspectra I and II enable sequential resonance assignment in combination with HNNCAHA and HNNCACB, respectively, by matching intraresidue and sequential l U a , 13 C α and 13 C β chemical shifts (Figure 8). (When considering 'nuclear spin relaxation time labeling' of peak pairs, subspectrum II derived from 13 C steady state magnetization provides largely redundant information when compared with subspectrum I. However, the observation of the central peaks allows direct matching of peak positions between subspectrum II, essentially a CBCA(CO)NHN spectrum, and HNNCACB (Fig. 6).) Moreover, this set of chemical shifts alone provides valuable information for amino acid type identification (Zimmerman et al., J. Mol. Biol., 269:592-610 (1997); Cavanagh et al., Protein NMR Spectroscopy. Academic Press, San Diego, (1996); Grzesiek et al., J. Biomol. NMR. 3:185-204 (1993), which are hereby incorporated by reference in their entirety). Complementary recording of 3D H α/β C α/β COHA and 3D HNN<CO,CA> contributes polypeptide backbone 13 C=O chemical shift measurements for establishing sequential assignments: the intraresidue correlation is obtained by ω^C^) peak pattern matching (Figures 9A-B) with 3D H α β C α β (CO)NHN, and the sequential correlation is inferred from 13 C α , 15 N and 1H N chemical shifts in 3D HNN<CO,CA> (Szyperski et al, I Biomol. NMR, 11 :387-405 (1998), which is hereby incorporated by reference in its entirety). Notably, even for medium-sized (non-deuterated) proteins this approach is superior to the use of a low sensitivity HNNCACO-type experiment (e.g., in combination with HNNCOCA), where the magnetization transfer via rapidly relaxing 13 C α relies on the rather small 15 N- 13 C α one-bond scalar coupling. Secondly, comparison of ω 1 ( 13 C α/β ) peak patterns with 3D HCCH-COSY (Figure 10) and TOCSY connects the C^/H^ chemical shifts with those of the aliphatic side chain spin systems (For Z-domain, complete side chain assignments were obtained for all but six residues using 3D HCCH-COSY only.) (Figures 10 and 11), while comparison of ω^C 13 ) peaks with 2D HBCB(CDCG)HD and subsequent linking with 1H δ chemical shifts detected in 2D 1H-TOCSY-relayed HCH-COSY affords assignment of the aromatic spin systems (Figure 12). Since for many amino acid residues the two β-protons exhibit non-degenerate chemical shifts, the connection of H α/β C α β (CO)NHN and HBCB(CDCG)HD or HCCH- COS Y/TOCS Y (Figure 7) may in fact often rely on comparison of three chemical shifts, i.e., δ(1H β2 ), δ( 1 H β3 ) and δ( 13 C β ). This consideration underscores the potential of recruiting β-proton chemical shifts for establishing sequential resonance assignments. [0179] The 'standard set' of nine experiments (labeled with asterisks in Table 2) as described in the above paragraph required 60 hours of instrument time for the Z-domain on our 600 MHz NMR system (Table 2). However, the minimal S/N ratios detected (Table 4) reveal that half of the measurement time would have been sufficient for backbone amide proton detected experiments, indicating that these spectra were still acquired in the sampling limited regime. (The lowest S/N peak ratios are around 5:1, which implies that a reduction of by could be afforded. A further indication of an inappropriately long measurement time is due to the fact that nearly all sequential connectivities relying on two-bond scalar couplings (Guntert et al., J. Biomol. NMR. 2:619-629 (1992), which is hereby incorporated by reference in its entirety) were observed in 3D HNNCAHA (Figure 7): nearly all 1H N , 15 N, 13 C α and 1H α backbone resonances of Z-domain could be assigned using this spectrum (Szyperski et al., J. Biomol. NMR. 11 :387-405 (1998), which is hereby incorporated by reference in its entirety) alone.) Hence, a nearly complete resonance assignment of the Z-domain could have been obtained from the standard set in about 40 hours, if the RD backbone experiments were conducted with a single transient per acquired FID. (The suite of experiments in Table 1 may provide complete resonance assignments of proteins, excluding only the side chain NH n moieties, the CH ε groups of histidinyl, and the CH ε3 , CH ζ2 ' 3 and CH η2 groups of tryptophanyl residues, which can be obtained as described in Yamazaki et al., J. Am. Chem. Soc. 115:11054-11055 (1993), which is hereby incorporated by reference in its entirety. Notably, the protein studied here does not contain tryptophan residues.) This outstandingly short measurement time needs to be compared with 1-3 weeks of measurement time that are currently routinely invested to assign medium-sized proteins. Concomitantly, the high redundancy for establishing sequential connectivities using this suite of experiments (six projected 4D, one 3D and two projected 3D experiments) greatly supports robust automated assignment. Importantly, the information encoded in each projected 4D spectrum cannot be obtained by simply recording two 3D spectra: in cases of chemical shift degeneracy a chemical shift quartuple is not equivalent to two shift triples. Example 6 - Sensitivity Profile Within the "Standard Set" of NMR Experiments [0180] It is desirable that the NMR experiments applied for protein resonance assignment in a high-throughput manner exhibit comparable sensitivity. This is because the prediction of the totally required measurement times is facilitated (roughly a multiple of the measurement time of an arbitrarily chosen single experiment) and the signal-to-noise ratios observed in the experiment conducted first allow one to readily adjust the (rather similar) measurement times of the remaining ones while the recording of the set of experiments is in progress. It is thus important to note that the sensitivity within the standard set of nine experiments (Table 2) varies by only about a factor of two when comparing peak pair detection in 3D H α/β C α/β (CO)NHN with relay COSY peak detection in 3D HCCH-TOCSY (Figure 5). Extraordinarily sensitive central peak detection in 3D HNN<CO,CA> represents the sole exception. However, the availability of extremely sensitive detection of (1H N , 15 N, 13 C=O) chemical shift triples is of high value for identification of spin systems (Zimmerman et al., J. Mol. Biol.. 269:592-610 (1997), which is hereby incorporated by reference in its entirety). In fact, this apparent exception thus neatly complements the even sensitivity profile of the remaining experiments. Example 7 - A "Minimal Set" of RD NMR Experiments [0181] For Z-domain, six RD NMR experiments were actually sufficient to provide the desired resonance assignments: 3D H /β C β (CO)NHN, 3D HNNCAHA. 3D HCCH-COSY / TOCSY, 2D HBCB(CDCG)HD and 2D 1H- TOCS Y-relayed HCH-COSY. This set of experiments was recorded within 36 hours of instrument time (Table 2), and can be considered as a 'minimal set' of RD NMR experiments for HTP resonance assignment of proteins up to around 10 kDa. For smaller proteins, the use of 3D HC(C-TOCSY-CO)NHN, 3D If p C p NHN, 3D HCCH-COSY, 2D HBCB(CDCG)HD and 2D 1H-TOCSY- relayed HCH-COSY represents a viable alternative to rapidly obtain assignments (Table 1). [0182] Although preferred embodiments have been depicted and described in detail herein, it will be apparent to those skilled in the relevant art that various modifications, additions, substitutions, and the like can be made without departing from the spirit of the invention and these are therefore considered to be within the scope of the invention as defined in the claims which follow.

Claims: WHAT IS CLAIMED: 1. A method of conducting a reduced dimensionality three-dimensional (3D) HA,CA,(CO),N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having two consecutive amino acid residues, i-1 and i: (1) an α-proton of amino acid residue i-1, (2) an α- carbon of amino acid residue i-1, 13 C α ;.ι; (3) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N ; -; and (4) a polypeptide backbone amide proton of amino acid residue i, 1 H N i, said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1 H α ,-ι and 13 C α ,-_ι of amino acid residue i-1 axe connected to the chemical shift evolutions of 15 N; and H N , of amino acid residue i, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α / .ι and 15 N; in a phase sensitive manner in two indirect time domain dimensions, tι( 13 C α ) and t 2 ( 15 N), respectively, and the chemical shift value of 1H N ,- in a direct time domain dimension, t 3 (1H N ), and (2) to cosine modulate the I3 C .ι chemical shift evolution in ( l3 C ) with the chemical shift evolution of 1 H α , -1 ; and processing the NMR signals to generate a 3D NMR spectrum with a primary peak pair derived from said cosine modulating, wherein (1) the chemical shift values of 15 N, and 1 H N ,- are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 (1H N ), respectively, and (2) the chemical shift values of 'H",- ! and 13 C α ,_j are measured in a frequency domain dimension, ω ! ( 13 C α ), by the frequency difference between the two peaks forming said primary peak pair and the frequency at the center of the two peaks, respectively. 2. The method according to claim 1, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of 15 N,- does not occur and said processing the NMR signals generates a two dimensional (2D) NMR spectrum with a peak pair wherein (1) the chemical shift value of 1H N is measured in a frequency domain dimension, ro 2 (1H N ), and (2) the chemical shift values of 'H" .. ! and 13 C α / .ι are measured in a frequency domain dimension, α>ι( 13 C α ), by the frequency difference between the two peaks forming said primary peak pair and the frequency at the center of the two peaks, respectively. 3. The method according to claim 1, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' ;-1 , occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 CYι in a phase sensitive manner in an indirect time domain dimension, t 4 ( I3 C), and said processing the NMR signals generates a four dimensional (4D) NMR spectrum with a peak pair wherein (1) the chemical shift values of I5 N,, 1H ,- and 13 C',.; are measured in three frequency domain dimensions, ω 2 ( 15 N), ω 3 (1H N ), and ω 4 ( I3 C), respectively, and (2) the chemical shift values of and 13 C™ .ι are measured in a frequency domain dimension, ωι( 13 C α ), by the frequency difference between the two peaks forming said peak pair and the frequency at the center of the two peaks, respectively. 4. The method according to claim 1, wherein said applying radiofrequency pulses is carried out under conditions effective to additionally cosine modulate the 13 C , -1 chemical shift evolution in tι( 13 C α ) with the chemical shift evolution of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' ;-1 , and said processing the NMR signals generates a 3D NMR spectrum with two secondary peak pairs wherein (1) each of the secondary peak pairs is derived from a different one of the peaks of the primary peak pair, and (2) the chemical shift value of 13 C',. 1 is measured along ω ! ( 13 C α ) by the frequency difference between the two peaks forming one of the secondary peak pairs. 5. The method according to claim 4, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α (-1 and 15 N,- in a phase sensitive manner in tι( 13 C α ) and t 2 ( 15 N) and the chemical shift value of 1H N ; in t 3 (1H N ), (2) to cosine modulate the 13 C α chemical shift evolution in t 1 ( 13 C α ) with the chemical shift evolution of 13 C'M, and (3) to avoid cosine modulating the 13 C ,.j chemical shift evolution in tϊ( 13 C α ) with the chemical shift evolution of 1 H α ,-ι, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with an additional secondary peak pair located between said two secondary peak pairs which measures the chemical shift values of 13 C' ;-1 and 13 C α .ι along ω 1 ( 13 C ), by the frequency difference between the two peaks forming the additional secondary peak pair and the frequency at the center of said two peaks, respectively. 6. The method according to claim 5, wherein said additional secondary peak pair is derived from 13 C α nuclear spin polarization. 7. The method according to claim 6, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IB, wherein a radiofrequency pulse is used to create transverse 1H α (-1 magnetization, and 1 H α , -1 magnetization is transferred to 13 C" .ι, to 15 N,, and to 1 H N / , where the NMR signal is detected. 8. The method according to claim 7, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2B to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2B, wherein phase φϊ of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal arid the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said two secondary peak pairs, and a second NMR subspectrum derived from said adding which contains said additional secondary peak pair. 9. The method according to claim 1, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α ;.ι and 15 N,- in a phase sensitive manner in t 1 ( 13 C α ) and t 2 ( 15 N) and the chemical shift value of 1 H N , in t 3 ( ! H N ), and (2) to avoid cosine modulating the 13 C α r-1 chemical shift evolution in t ! ( 13 C α ) with the chemical shift evolution of 1 H α , -1 for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with an additional peak located centrally between two peaks forming said primary peak pair which measures the chemical shift value of 13 C α !-1 along ωι ( 13 C α ). 10. The method according to claim 9, wherein said additional peak is derived from 13 C α nuclear spin polarization. 11. The method according to claim 10, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IB, wherein a radiofrequency pulse is used to create transverse 'H" - ! magnetization, which is transferred to 13 C , to 15 N ; -, and to ,, to generate the NMR signal. 12. The method according to claim 11, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2B to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2B, wherein phase φi of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said primary peak pair and a second NMR subspectrum derived from said adding which contains said additional peak located centrally between the two peaks forming said primary peak pair. 13. A method of conducting a reduced dimensionality three-dimensional (3D) H,C,-(C-TOCS Y-CO),N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having two consecutive amino acid residues, i-1 and i: (1) aliphatic protons of amino acid residue i-1, 1 H all ;. 1 ; (2) aliphatic carbons of amino acid residue i-1, 13 C all / .ι; (3) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N,-; and (4) a polypeptide backbone amide proton of amino acid residue i, 1H N ,, said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1 H all ,- 1 and of amino acid residue i-1 are connected to the chemical shift evolutions of 15 N,- and 1H N ,- of amino acid residue i, under conditions effective (1) to generate a NMR signal encoding the chemical shifts of 13 C all -ι and 15 N,- in a phase sensitive manner in two indirect time domain dimensions, t 1 ( 13 C ah ) and t ( 15 N), respectively, and the chemical shift of 1H N / in a direct time domain dimension, t 3 (1H N ), and (2) to cosine modulate the chemical shift evolutions of in t ! ( 13 C aIi ) with the chemical shift evolutions of 'H 31 ^; and processing the NMR signals to generate a 3D NMR spectrum with peak pairs derived from said cosine modulating wherein (1) the chemical shift values of ls N,and 1 H N 7 - are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 (1H N ), respectively, and (2) the chemical shift values of 1 H aIl / _ι and ^C 3 ' 1 ,- ! are measured in a frequency domain dimension, ω \ ( 13 C ah ), by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 14. The method according to claim 13, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of 15 N, does not occur and said processing the NMR signals generates a two dimensional (2D) NMR spectrum with peak pairs wherein (1) the chemical shift value of 1 H li j is measured in a frequency domain dimension, ro 2 (1H N ), and (2) the chemical shift values of 'H 3 ' 1 ,-. ! and 13 C all ;-1 are measured in a frequency domain dimension, ω ! ( 13 C a '), by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 15. The method according to claim 13, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' / _ι, occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C' / _ι in a phase sensitive manner in an indirect time domain dimension, t 4 ( C), and said processing the NMR signals generates a four dimensional (4D) NMR spectrum with variant peak pairs wherein (1) the chemical shift values of 15 N,-, 1H N ,- and 13 C' . ! are measured in three frequency domain dimensions, ω ( 15 N), ω 3 (1H N ), and ω 4 ( 13 C), respectively, and (2) the chemical shift values of 1H ali (-1 and 13 C ali ;-1 are measured in a frequency domain dimension, ωι( 13 C ah ), by the frequency differences between the two peaks forming said variant peak pairs and the frequencies at the center of the two peaks, respectively. 16. The method according to claim 13, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C a Vι and 15 N,- in a phase sensitive manner in tj( 13 C a ) and t 2 ( 15 N) and the chemical shift value of 1H N ,- in t 3 (1H N ), and (2) to avoid cosine modulating the chemical shift evolutions of 13 C ali ;-1 in ( 13 C i ) with the chemical shift evolution of 1 H α , -1 for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with additional peaks located centrally between said peak pairs which measure the chemical shift values of 13 C ah (-1 along ω!( 13 C al1 ). 17. The method according to claim 16, wherein said additional peaks are derived from 13 C ah nuclear spin polarization. 18. The method according to claim 17, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IC, wherein a radiofrequency pulse is used to create transverse 1 H a,, I -_ι magnetization, and 1 H all /-1 magnetization is transferred to "C^i, to 13 C α M , to 13 C' M , to 15 N,-, and to 1H N ,-, where the NMR signal is detected. 19. The method according to claim 18, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2C to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2C, wherein phase φ] of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said peak pairs, and a second NMR subspectrum derived from said adding which contains said additional peaks located centrally between said peak pairs. 20. A method of conducting a reduced dimensionality three-dimensional (3D) nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having an amino acid residue, i: (1) a β-proton of amino acid residue i, 1H β ,; (2) a β-carbon of amino acid residue i, 13 C β ,-; (3) an α-proton of amino acid residue i, l U a ,; (A) an α-carbon of amino acid residue i, 13 C α ; and (5) 1 " a polypeptide backbone carbonyl carbon of amino acid residue i, C'„ said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 'if 1 ,-, 1H β ,-, 13 C α ,-, and 13 C β ,- are connected to the chemical shift evolution of 13 C',-, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α ;, 13 C β ,- and 13 C' ; - in a phase sensitive manner in two indirect time domain dimensions, ti^C^) and t ( 13 C), respectively, and the chemical shift value of 1 H ,- in a direct time domain dimension, t 3 (1H α ), and (2) to cosine modulate the chemical shift evolutions of 13 C α and 13 C β ,- in t^C^) with the chemical shift evolutions of 1 H α ; and 1H β ,-, respectively; and processing the NMR signals to generate a 3D NMR spectrum with peak pairs derived from said cosine modulating wherein (1) the chemical shift values of 13 C',and 1H α ,- are measured in two frequency domain dimensions, ω 2 ( 13 C) and ω 3 (1H α ), respectively, and (2) (i) the chemical shift values of 'H", and 1H β ,- are measured in a frequency domain dimension, ω ! ( 13 C α β ), by the frequency differences between the two peaks forming said peak pairs, and (ii) the chemical shift values of 13 C α / , and 13 C β ,- are measured in a frequency domain dimension, ω ϊ ( 13 C β ), by the frequencies at the center of the two peaks forming said peak pairs. 21. The method according to claim 20, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of 13 C',- does not occur and said processing the NMR signals generates a two dimensional (2D) NMR spectrum with peak pairs wherein (1) the chemical shift value of 1 H α , is measured in a frequency domain dimension, ω (1H α ), and (2) (i) the chemical shift values of 'H™,- and 1H β ,- are measured in a frequency domain dimension, ω 1 ( 13 C /β ), by the frequency differences between two peaks forming said peak pairs, respectively, and (ii) the chemical shift values of 13 C α ,-, and 13 C β ,- are measured in a frequency domain dimension, ω 1 ( I3 C /β ), by the frequencies at the center of the two peaks forming said peak pairs. 22. The method according to claim 20 wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α ,, 13 C β ; and 15 N ; - in a phase sensitive manner in 3 C a ) and t 2 ( 15 N) and the chemical shift value of 1 H α ,- in t 3 (1H α ), and (2) to avoid cosine modulating the chemical shift evolutions of 13 C α ,- and 13 C β ,- in ti^C^) with the chemical shift evolutions of 'H™ and 1H β , for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with additional peaks located centrally between the two peaks forming said peak pairs which measure the chemical shift values of 13 C α ,- and 13 C β , along ω^C^). 23. The method according to claim 22, wherein said additional peaks are derived from 13 C α and 13 C β nuclear spin polarization. 24. The method according to claim 23, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IE, wherein a radiofrequency pulse is used to create transverse 'H",- and 1 H β / - magnetization, and 1 H α ; - and 1H 13 polarization is transferred to 13 C α ; - and 13 C β *, to 13 C',-, and back to 1H α / , where the NMR signal is detected. 25. The method according to claim 24, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2E to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2E, wherein phase φ] of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said peak pairs, and a second NMR subspectrum derived from said adding which contains said additional peaks located centrally between the two peaks forming said peak pairs. 26. A method of conducting a reduced dimensionality three-dimensional (3D) H α/β ,C α/p ,N,HN nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for the following nuclei of a protein molecule having an amino acid residue, i: (1) a β-proton of amino acid residue i, 'H^; (2) a β-carbon of amino acid residue i, 3 C β ,-; (3) an α-proton of amino acid residue i, l H α ,-; (4) an α-carbon of amino acid residue i, 3 C α ,-; (5) a polypeptide backbone amide nitrogen of amino acid residue i, 15 N,; and (6) a polypeptide backbone amide proton of amino acid residue i, 1H N , said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1H α , 1H β ,-, 13 C α , and 13 C β ,- are connected to the chemical shift evolutions of 15 N; and 1H N ,, under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C α ; -, 13 C β ,- and 15 N,- in a phase sensitive manner in two indirect time domain dimensions, tι( 3 C a/ ^) and t 2 ( 15 N), respectively, and the chemical shift value of 1 H N ,- in a direct time domain dimension, t 3 (1H N ), and (2) to cosine modulate the chemical shift evolutions of 13 C α ,- and 13 C β in t 1 ( 13 C α β ) with the chemical shift evolutions of 1H α , and 1 H β ,-, respectively; and processing the NMR signals to generate a 3D NMR spectrum with peak pairs derived from said cosine modulating wherein (1) the chemical shift values of 15 N, and 1H N ; are measured in two frequency domain dimensions, ω 2 ( 15 N) and ω 3 (1H N ), respectively, and (2) (i) the chemical shift values of 1 H ; and 1H β ,- are measured in a frequency domain dimension, ω 1 ( 13 C α/β ), by the frequency differences between the two peaks forming said peak pairs, and (ii) the chemical shift values of 13 C ,-, and 13 C β ,- are measured in a frequency domain dimension, by the frequencies at the center of said two peaks forming said peak pairs. 27. The method according to claim 26, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of 15 N,- does not occur and said processing the NMR signals generates a two dimensional (2D) NMR spectrum with peak pairs wherein (1) the chemical shift value of 1H N , is measured in a frequency domain dimension, ω 2 (1H N ), and (2) (i) the chemical shift values of 1 H α ; - and 1H β ,- are measured in a frequency domain dimension, by the frequency differences between the two peaks forming said peak pairs, and (ii) the chemical shift values of 13 C α ,-, and 13 C β , are measured in a frequency domain dimension, ωι( 13 C α/ ' 5 )- by the frequencies at the center of the two peaks forming said peak pairs. 28. The method according to claim 26, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C α „ 13 C β , and 15 N,- in a phase sensitive manner in fι( 13 C α p ) and t 2 ( 15 N) and the chemical shift value of 1H N / in t 3 (1H N ), and (2) to avoid cosine modulating the chemical shift evolutions of 13 C α , and 13 C β ,- in tι( 13 C ot p ) with the chemical shift evolutions of 1 H α ,- and 1H β ; for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with additional peaks located centrally between the two peaks forming said peak pairs which measure the chemical shift values of 13 C α ,- and 13 C β ,- along 29. The method according to claim 28, wherein said additional peaks are derived from 13 C α and 13 C β nuclear spin polarization. 30. The method according to claim 29, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IF, wherein a radiofrequency pulse is used to create transverse 1H α , and 1H β ,- magnetization, and 1H α ,- and ! H P , magnetization is transferred to 13 C α ,- and 13 C β ,-, to 15 N,-, and to 1 H N / , where the NMR signal is detected. 31. The method according to claim 30, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2F to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2F, wherein phase φi of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said peak pairs, and a second NMR subspectrum derived from said adding which contains said additional peaks located centrally between the two peaks forming said peak pairs. 32. A method of conducting a reduced dimensionality three-dimensional (3D) H,C,C,H-COSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1 H m , l3 ", ! H", and 13 C" of a protein molecule wherein m and n indicate atom numbers of two CH, CH 2 or CH 3 groups that are linked by a single covalent carbon-carbon bond in an amino acid residue, said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1H W and 13 C" are connected to the chemical shift evolutions of 1 H" and 13 C", under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C m and 13 C" in a phase sensitive manner in two indirect time domain dimensions, t 1 ( 13 C /M ) and t 2 ( 13 C"), respectively, and the chemical shift value of 1H" in a direct time domain dimension, t 3 (1H"), and (2) to cosine modulate the chemical shift evolution of 13 C" in t ! ( 13 C ) with the chemical shift evolution of 1H W ; and processing the NMR signals to generate a 3D NMR spectrum with peak pairs derived from said cosine modulating wherein (1) the chemical shift values of 13 C" and ! H" are measured in-two frequency domain dimensions, ω ( 13 C") and ω 3 ( 1 H"), respectively, and (2) the chemical shift values of 1 H W and 13 C are measured in a frequency domain dimension, ωι( 13 C m ), by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 33. The method according to claim 32, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of 13 C" does not occur and said processing the NMR signals generates a two dimensional (2D) NMR spectrum with peak pairs wherein (1) the chemical shift value of 1H" is measured in a frequency domain dimension, ω (1H"), and (2) the chemical shift values of l Jϊ m and 13 C" are measured in a frequency domain dimension, ω^ C m ), by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 34. The method according to claim 32, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C m and 13 C" in a phase sensitive manner in tι( 13 C m ) and t 2 ( 13 C") and the chemical shift value of ! H" in t 3 (1H), and (2) to avoid cosine modulating the chemical shift evolution of 13 C m in tι( l3 C m ) with the chemical shift evolution of 1H W for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with additional peaks located centrally between the two peaks forming said peak pairs which measure the chemical shift value of 13 C" along ωι( 13 C m ). 35. The method according to claim 34, wherein said additional peaks are deriyed from 13 C m nuclear spin polarization. 36. The method according to claim 35, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IH, wherein a radiofrequency pulse is used to create transverse 1H" 1 magnetization, and H m magnetization is transferred to 13 C", to 13 C", and to 1H", where the NMR signal is detected. 37. The method according to claim 36, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2H to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2H, wherein phase φi of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said peak pairs, and a second NMR subspectrum derived from said adding which contains said additional peaks located centrally between the two peaks forming said peak pairs. 38. A method of conducting a reduced dimensionality three-dimensional (3D) H,C,C,H-TOCSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for l U m , l3 C m , 1H", and 13 C" of a protein molecule wherein m and n indicate atom numbers of two CH, CH 2 or CH 3 groups that may or may not be directly linked by a single covalent carbon-carbon bond in an amino acid residue, said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1H m and 13 C W are connected to the chemical shift evolutions of 1H" and 13 C", under conditions effective (1) to generate NMR signals encoding the chemical shift values of 13 C" and 13 C" in a phase sensitive manner in two indirect time domain dimensions, tι( 13 C") and t 2 ( 13 C"), and the chemical shift value of 1H" in a direct time domain dimension, t 3 ( 1 H"), and (2) to cosine modulate the chemical shift evolution of 13 C" in tι( 13 C w ) with the chemical shift evolution of l H m ; and processing the NMR signals to generate a 3D NMR spectrum with peak pairs derived from said cosine modulating wherein (1) the chemical shift values of 13 C" and 1H" are measured in two frequency domain dimensions, ω ( 13 C") and ω 3 ( 1 H"), respectively, and (2) the chemical shift values of 1H" 1 and 13 C m are measured in a frequency domain dimension, G>ι( 13 C m ), by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 39. The method according to claim 38, wherein said applying radiofrequency pulses is carried out so that the chemical shift evolution of 13 C" does not occur and said processing the NMR signals generates a two dimensional (2D) NMR spectrum with peak pairs wherein (1) the chemical shift value of ! H" is measured in a frequency domain dimension, ω (1H"), and (2) the chemical shift values of 1H m and 13 C W are measured in a frequency domain dimension, by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 40. The method according to claim 38, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift values of 13 C m and 13 C" in a phase sensitive manner in tι( 13 C m ) and t 2 ( 13 C") and the chemical shift value of 1H" in t 3 (1H"), and (2) to avoid cosine modulating the chemical shift evolution of 13 C m in tι( l3 ") with the chemical shift evolution of 1H W for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 3D NMR spectrum with additional peaks located centrally between the two peaks forming said peak pairs which measure the chemical shift value of 13 C" along ωι( I3 C"). 41. The method according to claim 40, wherein said additional peaks are derived from 13 C m nuclear spin polarization. 42. The method according to claim 41 , wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure II, wherein a radiofrequency pulse is used to create transverse 1H m magnetization, and 1H m magnetization is transferred to 13 C m , to 13 C", and to 1H", where the NMR signal is detected. 43. The method according to claim 42, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 21 to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 21, wherein phase φj of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: ι adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said peak pairs, and a second NMR subspectrum derived from said adding which contains said additional peaks located centrally between the two peaks forming said peak pairs. 44. A method of conducting a reduced dimensionality two-dimensional (2D) HB,CB,(CG,CD),HD nuclear magnetic resonance (NMR) experiment by measuring the, chemical shift values for the following nuclei of a protein molecule : (1) a β-proton of an amino acid residue with an aromatic side chain, 1H β ; (2) a β-carbon of an amino acid residue with an aromatic side chain, 13 C β ; and (3) a δ-proton of an amino acid residue with an aromatic side chain, said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1H β and 13 C β are connected to the chemical shift evolution of 1H δ , under conditions effective (1) to generate NMR signals encoding the chemical shift value of 13 C β in a phase sensitive manner in an indirect time domain dimension, tι( 13 C β ), and the chemical shift value, of 1H δ in a direct time domain dimension, t 2 (1H δ ), and (2) to cosine modulate the chemical shift evolution of 13 C β in t 1 ( 13 C β ) with the chemical shift evolution of 'H 13 ; and processing the NMR signals to generate a 2D NMR spectrum with a peak pair derived from said cosine modulating wherein (1) the chemical shift value of H is measured in a frequency domain dimension, ω 2 ( ! H δ ), and (2) the chemical shift values of 1H β and 13 C β are measured in a frequency domain dimension, ωι( 13 C β ), by the frequency difference between the two peaks forming said peak pair and the frequency at the center of the two peaks, respectively. 45. The method according to claim 44, wherein said applying radiofrequency pulses is carried out so that: (i) the chemical shift evolution of a δ-carbon of an amino acid residue with an aromatic side chain, C , occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C δ in a phase sensitive manner in an indirect time domain dimension, t ( C ), and said processing the NMR signals generates a three dimensional (3D) NMR spectrum with a peak pair wherein (1) the chemical shift values of H and C are measured in two frequency domain dimensions, ω 2 ( H ) and ω 3 ( C ), respectively, and (2) the chemical shift values of 1H β and 13 C β are measured in a frequency domain dimension, ω ! ( 13 C β ), by the frequency difference between the two peaks forming said peak pair and the frequency at the center of the two peaks, respectively; or (ii) the chemical shift evolution of a γ-carbon of an amino acid residue with an aromatic side chain, 13 C γ occurs under conditions effective to generate NMR signals encoding the chemical shift value of 13 C γ , in a phase sensitive manner in an indirect time domain dimension, t 3 ( 13 C γ ), and said processing the NMR signals generates a three dimensional (3D) NMR spectrum with a peak pair wherein (1) the chemical shift values of 1H δ and I3 C γ are measured in two frequency domain dimensions, ω ( ! H δ ) and ω 3 ( 13 C γ ), respectively, and (2) the chemical shift values of 1H 13 and 13 C β are measured in a frequency domain dimension, ω ϊ ( 13 C β ), by the frequency difference between the two peaks forming said peak pair and the frequency at the center of the two peaks, respectively. 46. The method according to claim 44, wherein said applying radiofrequency pulses is carried out under conditions effective (1) to generate an additional NMR signal encoding the chemical shift value of 13 C β in a phase sensitive manner in t!( 13 C β ) and the chemical shift value of ! H δ in t 2 ( ! H δ ), and (2) to avoid cosine modulating the chemical shift evolution of 13 C β in tι( u &) with the chemical shift evolution of 1H β for the additional NMR signal, and said processing the NMR signals and the additional NMR signal generates a 2D NMR spectrum with an additional peak located centrally between said peak pair which measure the chemical shift value of 13 C β along ωι( 13 C β ). 47. The method according to claim 46, wherein said additional peak is derived from 13 C β nuclear spin polarization. 48. The method according to claim 47, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure 1 J, wherein a radiofrequency pulse is used to create transverse 1H β magnetization, and 1H β magnetization is transferred to 13 C β , to 13 C δ , and to 1H δ , where the NMR signal is detected. 49. The method according to claim 48, wherein said applying radiofrequency pulses comprises: applying a first set of radiofrequency pulses according to the scheme shown in Figure 2J to generate a first NMR signal, and applying a second set of radiofrequency pulses according to the scheme shown in Figure 2J, wherein phase φi of the first 1H pulse is altered by 180° to generate a second NMR signal, said method further comprising: adding and subtracting the first NMR signal and the second NMR signal prior to said processing, whereby said processing the NMR signals generates a first NMR subspectrum derived from said subtracting which contains said peak pair, and a second NMR subspectrum derived from said adding which contains said additional peak located centrally between the two peaks forming said peak pair. 50. A method of conducting a reduced dimensionality two-dimensional (2D) H,C,H-COSY nuclear magnetic resonance (NMR) experiment by measuring the chemical shift values for 1H 7 ", 13 C", and 1H" of a protein molecule wherein m and n indicate atom numbers of two CH, CH 2 or CH 3 groups in an amino acid residue, said method comprising: providing a protein sample; applying radiofrequency pulses to the protein sample which effect a nuclear spin polarization transfer wherein the chemical shift evolutions of 1H ∞ and l3 C m are connected to the chemical shift evolution of 1H", under conditions effective (1) to generate NMR signals encoding the chemical shift value of 13 C m in a phase sensitive manner in an indirect time domain dimension, tι( 13 C m ), and the chemical shift value of 1H" in a direct time domain dimension, t2( 1 H"), and (2) to cosine modulate the chemical shift evolution of 13 C in tι( l3 C m ) with the chemical shift evolution of 1H W ; and processing the NMR signals to generate a 2D NMR spectrum with peak pairs derived from said cosine modulating wherein (1) the chemical shift value of 1H" is measured in a frequency domain dimension, ω 2 ( 1 H"), and (2) the chemical shift values of 1H W and 13 C" are measured in a frequency domain dimension, ωι( 13 C"), by the frequency differences between the two peaks forming said peak pairs and the frequencies at the center of the two peaks, respectively. 51. The method according to claim 50, wherein said applying radiofrequency pulses effects a nuclear spin polarization transfer according to Figure IK, wherein a radiofrequency pulse is used to create transverse 1 ϊJ magnetization, and 1H 7 " polarization is transferred to l3 C m , to 1 H TO , and to 1H", where the NMR signal is detected. 52. The method according to claim 51 , wherein said applying radiofrequency pulses is carried out according to the scheme shown in Figure 2K. 53. A method for sequentially assigning chemical shift values of an α-proton, 1 H α , an α-carbon, 13 C α , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule comprising: providing a protein sample; conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample comprising: (1) a RD three dimensional (3D) HA,CA,(CO),N,HN NMR experiment to measure and connect chemical shift values of the α- proton of amino acid residue i-1, 1H α M, the α-carbon of amino acid residue i-1, 13 C α ;-1 , the polypeptide backbone amide nitrogen of amino acid residue i, 15 N,, and the polypeptide backbone amide proton of amino acid residue i, 1H N ,- and (2) a RD 3D HNNCAHA NMR experiment to measure and connect the chemical shift values of the α-proton of amino acid residue i, 1H / , the α-carbon of amino acid residue i, 13 C α ,-, 15 N,-, and 1H N ,-; and obtaining sequential assignments of the chemical shift values of 1 H α , 13 C α , 15 N, and 1H N by (i) matching the chemical shift values of and 13 C ;-ι with the chemical shift values of 1H α ; and 13 C α ; , (ii) using the chemical shift values of 1 H α , -1 and 13 C α w to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using said chemical shift values to locate secondary structure elements within the polypeptide chain. 54. The method according to claim 53 further comprising: subjecting the protein sample to a RD 3D H α β C α/β (CO)NHN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i-1, 1 H p i _ι, the β-carbon of amino acid residue i-1, 13 C β , 1H α -ι, 13 C α M , 15 N,-, and 1H N ,-; and obtaining sequential assignments of the chemical shift values of 1H β and 13 C β by using the chemical shift values of 1H ;-1 and 13 C β /.ι to identify the type of amino acid residue i-1. 55. The method according to claim 54 further comprising: subjecting the protein sample to a RD 3D H α/β ,C α β ,CO,HA NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1H β ,-, the β-carbon of amino acid residue i, 13 C β ,-, 1H α ,, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C 7 -; and obtaining sequential assignments of the chemical shift value of 13 C',- by matching the chemical shift values of 1H 13 ,-, 13 C β / , 1H α , and 13 C α ,- measured by said RD 3D H α β ,C α/β ,CO,HA NMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , 'H", 13 C α , 15 N, and 1H N measured by said RD 3D HA 5 CA,(CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, and RD 3D H α/β C α/β (CO)NHN NMR experiment. 56. The method according to claim 54 further comprising: subjecting the protein sample to a RD 3D H α/β ,C α β ,N,HN NMR experiment to measure and connect the chemical shift values of 1 H β , 13 C β ,-, l Jϊ a j, 13 C°\-, 15 N,-, and 1H N ,-; and obtaining sequential assignments by matching the chemical shift values of 1H β ,-, ,3 C β ,-, 1H α ,-, and 13 C α ,- with the chemical shift values of 1 H β ;-1 , 13 C β M , 1 H α , -1 , and 13 C α ,.ι measured by said RD 3D H α/β C α/β (CO)NHN NMR experiment. 57. The method according to claim 54 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to measure and connect the chemical shift value of 13 C β ; -, 13 C α f , 15 N,-, and 1 H N ,-; and obtaining sequential assignments by matching the chemical shift values of 13 C β ; and 13 C α ,- measure by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β M and 13 C α measured by said RD 3D H α β C α/β (CO)NHN NMR experiment. 58. The method according to claim 54 further comprising: subjecting the protein sample to a RD two-dimensional (2D) HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 1H β / .ι, 13 C β , and a δ-proton of amino acid residue i-1 with an aromatic side chain, 1 H δ !-1 ; and obtaining sequential assignments by (i) matching the chemical shift values of 1 H β M and 13 C β M measured by said RD 2D HB, CB, (CG,CD), HD NMR experiment with the chemical shift values of 1H β and 13 C β measured by said RD 3D H α β C α β (CO)NHN NMR experiment, (ii) using said chemical shift values to identify amino acid residue i as having an aromatic side chain, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along said polypeptide chain. 59. The method according to claim 54 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, 1H ah ;, and aliphatic carbons of amino acid residue i, 13 C ali ,-; and obtaining sequential assignments of the chemical shift values of 1 H all 7 - and 13 C di by (i) matching the chemical shift values of 1H β ,, 13 C β ,-, 1 H α , and I3 C α ,- measured using said RD 3D H,C,C,H-COSY NMR experiment or RD 3D H,C,C,H-TOCSY RD NMR experiment with the chemical shift values of 1H β , 13 C β , 1H α , and 13 C α measured by said RD 3D HA,CA,(CO),N,HN NMR experiment, RD 3D HNNCAHA NMR experiment, and RD 3D H ot/β C α/β (CO)NHN NMR experiment and (ii) using the chemical shift values of 1H ali ,- and 13 C a , to identify the type of amino acid residue i. 60. The method according to claim 53 further comprising: subjecting the protein sample to a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 CYι, 13 C α ,-, 15 N,-, and 1 H N ,-; and obtaining sequential assignments of the chemical shift value of C Yi by matching the chemical shift value of 13 C α ,- measured by said RD 3D HNN<CO.CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by said RD 3D HA,CA,(CO),N,HN NMR experiment and RD 3D HNNCAHA NMR experiment. 61. The method according to claim 53 further comprising: subjecting the protein sample to (i) a RD 3D H α/p ,C α/β ,CO,HA NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1 H β ,-, the β-carbon of amino acid residue i, 13 C β ; , the α-proton of amino acid residue i, 'HY the α-carbon of amino acid residue i, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C\- and (ii) a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of 13 CY the α-carbon of amino acid residue i+1, 13 C α /+ ι, the polypeptide backbone amide nitrogen of amino acid residue i+1, 15 N, +l3 and the polypeptide backbone amide proton of amino acid residue i+1, 1 H N , +1 ; and obtaining sequential assignments by matching the chemical shift value of 13 C',- measured by said RD 3D HNN<CO,CA> NMR experiment with the chemical shift value of 13 C',- measured by said RD 3D H α β ,C α/β ,CO,HA NMR experiment. 62. The method according to claim 53, further comprising: subjecting the protein sample to a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i-1, 1 H all . 1 , aliphatic carbons of amino acid residue i-1, 13 C al Vι, 15 N,-, and 1 H N ,; and obtaining sequential assignments of the chemical shift values of H a .ι and l3 C ai i.i for amino acid residues i having unique pairs of 15 N,- and 1 H N , chemical shift values by matching the chemical shift values of 1H α and 13 C α measured by said RD 3D HNNCAHA NMR experiment and RD 3D HA,CA,(CO),N,HN NMR experiment with the chemical shift values of 1H α ;-1 and "CVi measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and using the 1 H all /-1 and 13 C all 7-1 chemical shift values to identify the type of amino acid residue i-1. 63. The method according to claim 53 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, H ah ,-, and aliphatic carbons of amino acid residue i, ^C 3 * 1 ,-; and obtaining sequential assignments of the chemical shift values of 1H 311 / and 13 C 3h , by (i) matching the chemical shift values of 1 H α ,- and 13 C α ; measured using said RD 3D H,C,C,H-COSY NMR experiment or RD 3D H,C,C,H-TOCSY RD NMR experiment with the chemical shift values of 1H α and 13 C α measured by said RD 3D HA,CA,(CO),N,HN NMR experiment and RD 3D HNNCAHA NMR experiment and (ii) using the chemical shift values of 1H al1 ,- and 13 C al1 ,-, to identify the type of amino acid residue i. 64. A method for sequentially assigning chemical shift values of a β-proton, Η β , a β-carbon, 13 C β , an α-proton, 1H , an α-carbon, 13 C α , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule comprising: providing a protein sample; conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample comprising: (1) a RD three-dimensional (3D) H α/β C α/β (CO)NHN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i-1, W , the β-carbon of amino acid residue i-1, 13 C β - t , the α-proton of amino acid residue i-1, 'HΥi, the α-carbon of amino acid residue i-1, 13 C°Yι, the polypeptide backbone amide nitrogen of amino acid residue i, 15 N,-, and the polypeptide backbone amide proton of amino acid residue i, 1H N , and (2) a RD 3D H α/β ,C α/β ,N,HN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1 H β ,-, the β-carbon of amino acid residue i, 13 C β ,, the α-proton of amino acid residue i, 1 H α ,-, the α-carbon of amino acid residue i, 13 C α ,-, 15 N,-, and 1H N ,; and obtaining sequential assignments of the chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N by (i) matching the chemical shift values of the α- and β-protons of amino acid residue i-1, 1 H α/β , -1 , and the α- and β-carbons of amino acid residue i-1, 13 C α β . l5 with the chemical shift values of 'H"^- and ^C^ 13 ,-, (ii) using the chemical shift values of 1 H α/β , -1 and '^^.i to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using said chemical shift values to locate secondary structure elements within the polypeptide chain. 65. The method according to claim 64 further comprising: subjecting the protein sample to a RD 3D HA.CA.(CO).N.HN NMR experiment (i) to measure and connect chemical shift values of ΗΥi, 13 CYι, 15 N,, and 1H N ,- and (ii) to distinguish between NMR signals for 1 H α / 13 C α and 1H β / 13 C β measured in said RD 3D H α/β C α β (CO)NHN NMR experiment and RD 3D H α β ,C α/β ,N,HN NMR experiment. 66. The method according to claim 64 further comprising: subjecting the protein sample to a RD 3D H α β ,C α β ,CO,HA NMR experiment to measure and connect the chemical shift values of 1H β , 13 C β ,-, 1 H < Y 13 C α ,, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',; and obtaining sequential assignments of the chemical shift value of C, by matching the chemical shift values of 1H β ,, 13 C β ; , 1HΥ and 13 C α ,- measured by said RD 3D jj α β ^ α/β O,HA NMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , 1H α , 13 C α , 15 N, and 1H N measured by said RD 3D H α/β C α β (CO)NHN NMR experiment and RD 3D H α/β ,C α/β ,N,HN NMR experiment. 67. The method according to claim 64 further comprising: subjecting the protein sample to a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 CYι, 13 CΥ 15 N ; -, and 1H N ,-; and obtaining sequential assignments of the chemical shift value of 13 C' ;-1 by matching the chemical shift value of 13 C α ; measured by said RD 3D HNN<CO.CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by said RD 3D H α/β C α β (CO)NHN NMR experiment and RD 3D H α β ,C α β ,N,HN NMR experiment. 68. The method according to claim 64 further comprising: subjecting the protein sample to (i) a RD 3D If /p £ α p ,CO > HA NMR experiment to measure and connect the chemical shift values of 1 H β ,, 13 C β ; -, 1H α ;, 13 C α ; -, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',- and (ii) a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of 13 C',-, the α-carbon of amino acid residue i+1, 13 C α ;+1 , the polypeptide backbone amide nitrogen of amino acid residue i+1, 15 Nj + ι, and the polypeptide backbone amide proton of amino acid residue i+1, 1H N H-ι; and obtaining sequential assignments by matching the chemical shift value of 13 C',- measured by said RD 3D HNN<CO,CA> NMR experiment with the chemical shift value of 13 C, measured by said RD 3D H α β ,C α β ,CO,HA NMR experiment. 69. The method according to claim 64 further comprising: subjecting the protein sample to a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of 1 H all !-1 , 13 C all , 15 N;, and 1H N ,-; and obtaining sequential assignments of the chemical shift values of 1H a!l , -1 and 13 C al, M for amino acid residues i having unique pairs of 15 N; and 1 H N ,- chemical shift values by matching the chemical shift values of 1H β , 13 C β , 1H α , and 13 C α measured by said RD 3D H α/β C α/β (CO)NHN NMR experiment and RD 3D H α β ,C α/β ,N,HN NMR experiment with the chemical shift values of WM, 13 C P , 1HΥ!, and 13 C α ;-1 measured by said RD 3D H,C,(C- TOCSY-CO),N,HN NMR experiment and using the 1 H ali i-1 and 13 C ali M chemical shift values to identify the type of amino acid residue i-1. 70. The method according to claim 64 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to measure and connect the chemical shift value of 13 C β ,, 13 C α ; , 15 N,-, and 1H N ,-; and obtaining sequential assignments by matching the chemical shift values of 13 C β ,- and 13 C α ,- measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β (-1 and 13 C e M measured by said RD 3D H α β C α β (CO)NHN NMR experiment. 71. The method according to claim 64 further comprising: subjecting the protein sample to a RD two-dimensional (2D) HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 1H β ,, 13 C β ,-, and a δ-proton of amino acid residue i with an aromatic side chain, 'H 6 ,-; and obtaining sequential assignments by (i) matching the chemical shift values of 1H β , and 13 C β ,- measured by said RD 2D HC, CB, (CG, CD), HDNMR experiment with the chemical shift values of 1H β and 13 C β measured by said RD 3D H α β C α/β (CO)NHN NMR experiment and RD 3D H α/β ,C α/β ,N,HN NMR experiment, (ii) using said chemical shift values to identify amino acid residue i as having an aromatic side chain, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along said polypeptide chain. 72. The method according to claim 64, further comprising: subjecting the protein sample to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, 1 H ah , and aliphatic carbons of amino acid residue i, 13 C al1 ,; and obtaining sequential assignments of the chemical shift values of 'H 31 ',- and 13 C aI \- by (i) matching the chemical shift values of 1H β ,-, 13 C β ,-, 1HΥ and 13 C α ,- measured using said RD 3D H,C,C,H-COSY NMR experiment or RD 3D H,C,C,H-TOCSY RD NMR experiment with the chemical shift values of 1H β , 13 C β , 1 H a , and 13 C α measured by said RD 3D H α/β C α/β (CO)NHN NMR experiment and RD 3D H α/β ,C α/β ,N,HN NMR experiment, and (ii) using the chemical shift values of 1 H ah ,- and 13 C al1 ,-, to identify the type of amino acid residue i. 73. A method for sequentially assigning the chemical shift values of aliphatic protons, 1 H ah , aliphatic carbons, 13 C a , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, ! H N , of a protein molecule comprising: providing a protein sample; conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample comprising: (1) a RD three-dimensional (3D) H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of the aliphatic protons of amino acid residue i-1, 1 H all ,-ι, the aliphatic carbons of amino acid residue i-1, 13 C all ,-_ι, the polypeptide backbone amide nitrogen of amino acid residue i, 15 N„ and the polypeptide backbone amide proton of amino acid residue i, 1H N , and (2) a RD 3D H α/β ,C α/β ,N,HN NMR experiment to measure and connect the chemical shift values of the β-proton of amino acid residue i, 1H β ,-, the β-carbon of amino acid residue i, 13 C β ,, the α-proton of amino acid residue i, 1H α , the α-carbon of amino acid residue i, 13 C α ,-, 15 N ; , and 1H N ,-; and obtaining sequential assignments of the chemical shift values of 1 H ah , 13 C ah , 15 N, and 1H N by (i) matching the chemical shift values of the α- and β-protons of amino acid residue i-1, 1 H α/β !-1 and the α- and β-carbons of amino acid residue i-1, 13 C α β ;-1 with the chemical shift values of 'H 0 ^,- and 13 C α β / of amino acid residue i, (ii) using the chemical shift values of 1 H all , -1 and 13 C 3l ',- -1 to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using said chemical shift values to locate secondary structure elements within the polypeptide chain. 74. The method according to claim 73 further comprising: subjecting the protein sample to a RD 3D H^C^CO^A NMR experiment to measure and connect the chemical shift values of 1H β , 13 C β , 'H" , 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',-; and obtaining sequential assignments of the chemical shift value of C, by matching the chemical shift values of 1 H β ,-, 13 C β ,-, 1 H α ; -, and 13 C α , measured by said RD 3D H α β ,C α β ,CO,HA NMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , 1 H α , 13 C α , 15 N, and 1H N measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D H α β ,C α/β ,N,HN NMR experiment. 75. The method according to claim 73 further comprising: subjecting the protein sample to a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 C' (-1 , 13 C α ,, 15 N,-, and 1H N ,-; and obtaining sequential assignments of the chemical shift value of C' ;-1 by matching the chemical shift value of 13 C" measured by said RD 3D HNN<CO.CA> NMR experiment with the sequentially assigned chemical shift values of 13 C α , 15 N, and 1H N measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D H α/β ,C α/β ,N,HN NMR experiment. 76. The method according to claim 73 further comprising: subjecting the protein sample to (i) a RD 3D H α β ,C α β ,CO,HA NMR experiment to measure and connect the chemical shift values of 1H β ,-, 13 C β ,-, 1 H α ,, 13 C α ; -, and a 1 " polypeptide backbone carbonyl carbon of amino acid residue i, C, and (ii) a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of 13 CY the α-carbon of amino acid residue i+1, 13 C α , +1 , the polypeptide backbone amide nitrogen of amino acid residue i+1, 15 N, +1 , and the polypeptide backbone amide proton of amino acid residue i+1, 1 H N /+1 ; and obtaining sequential assignments by matching the chemical shift value of 13 C; measured by said RD 3D HNN<CO,CA> NMR experiment with the chemical shift value of 13 C',- measured by said RD 3D H α β ,C α/β ,CO,HA NMR experiment. 77. The method according to claim 73 further comprising: subjecting the protein sample to a RD 3D H α β C α/β (CO)NHN NMR experiment (i) to measure and connect the chemical shift values of 1 H p ,-.ι, 13 C α p ,-.ι, 15 N,-, and 1H N 5 and (ii) to identify NMR signals for 1H α/β ; -b "C^M, 15 N,-, and 1H N ,- in said RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment. 78. The method according to claim 73 further comprising: subjecting the protein sample to a RD 3D HA,CA,(CO),N,HN NMR experiment (i) to measure and connect chemical shift values of 'HΥi, 13 C α , -1 , 15 N,, and 1H N , and (ii) to identify NMR signals for 1H α and 13 C α in said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D H α β ,C α/β ,N,HN NMR experiment. 79. The method according to claim 73 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to measure and connect the chemical shift value of 13 C β ,-, 13 C α / , 15 N ; , and 1H N ,-; and obtaining sequential assignments by matching the chemical shift values of 13 C P ; and 13 C°\- measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β ;-1 and 13 C α 7-1 measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. 80. The method according to claim 73 further comprising: subjecting the protein sample to a RD two-dimensional (2D) HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of 13 C β ,-, and a δ-proton of amino acid residue i with an aromatic side chain, 1H δ ,-; and obtaining sequential assignments by matching the chemical shift values of 1H β / and 13 C β ; measured by said RD 2D HB, CB, (CG, CD), HD NMR experiment with the chemical shift values of 1H β and 13 C β measured by said RD 3D H α β ,C α β ,N,HN NMR experiment and RD 3D H,C,(C-TOCS Y-CO),N,HN NMR experiment, using said chemical shift values to identify amino acid residue i as having an aromatic side chain, and mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along said polypeptide chain. 81. The method according to claim 73 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCSY NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, 1H ah ; and aliphatic carbons of amino acid residue i, 13 C ali ,-; and obtaining sequential assignments of the chemical shift values of 1H al1 ; and 13 C ali ,- by (i) matching the chemical shift values of 'H 3 ",- and 13 C ali ,- measured using said RD 3D H,C,C,H-COSY NMR experiment or RD 3D H,C,C,H-TOCSY NMR experiment with the chemical shift values of 1H ali and 13 C ali measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D H α β ,C α/β ,N,HN NMR experiment, and (ii) using the chemical shift values of 1 H al1 ,- and 13 C ah , to identify the type of amino acid residue i. 82. A method for sequentially assigning chemical shift values of aliphatic protons, 1 H ah , aliphatic carbons, 13 C a , a polypeptide backbone amide nitrogen, 15 N, and a polypeptide backbone amide proton, 1H N , of a protein molecule comprising: providing a protein sample; conducting a set of reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample comprising: (1) a RD three-dimensional (3D) H,C,(C-TOCSY-CO),N,HN NMR experiment to measure and connect the chemical shift values of the aliphatic protons of amino acid residue i-1, 1 H ah /.ι, the aliphatic carbons of amino acid residue i-1, l3 C a . \ , the polypeptide backbone amide nitrogen of amino acid residue i, 15 N,, and the polypeptide backbone amide proton of amino acid residue i, 1H N ,- and (2) a RD 3D HNNCAHA NMR experiment to measure and connect the chemical shift values of the α-proton of amino acid residue i, 1H α ;, the α-carbon of amino acid residue i, 13 C 15 N,-, and 1H N ;; and obtaining sequential assignments of the chemical shift values of 'H 3 ' 1 , 13 C ah , 15 N, and 1H N by (i) matching the chemical shift values of the α-proton of amino acid residue i-1, 'H b and the α-carbon of amino acid residue i-1, 13 C α (-1 , with the chemical shift values of 1 H α ,- and 13 C\ (ii) using the chemical shift values of 1 H ali , -1 and 13 C ali M to identify the type of amino acid residue i-1, and (iii) mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and using said chemical shift values to locate secondary structure elements within the polypeptide chain. 83. The method according to claim 82 further comprising: subjecting the protein sample to a RD 3D H^C^CO^A NMR experiment to measure and connect the chemical shift values of a β-proton of amino acid residue i, 1H β ;, a β-carbon of amino acid residue i, 13 C β ,, 1H α ,-, 13 C α ,-, and a polypeptide backbone carbonyl carbon of amino acid residue i, C',; and obtaining sequential assignments of the chemical shift value of 13 C\- by matching the chemical shift values of 1H 13 ,-, 13 C β ,-, 1H α ,-, and 13 C α ,- measured by said RD 3D H α/β ,C α/β ,CO,HANMR experiment with the sequentially assigned chemical shift values of 1H β , 13 C β , J H α , 13 C α , 15 N, and 1H N measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D HNNCAHA NMR experiment. 84. The method according to claim 82 further comprising: subjecting the protein sample to a RD 3D HNN<CO.CA> NMR experiment to measure and connect the chemical shift values of a polypeptide backbone carbonyl carbon of amino acid residue i-1, 13 CY U 13 C α ,-, 15 N,-, and 1H N ,-; and obtaining sequential assignments of the chemical shift value of C' 7-1 by matching the chemical shift value of 13 C α ; measured by said RD 3D HNN<CO,CA> NMR experiment with the sequentially assigned chemical shift values of I3 C α , 15 N, and 1H N measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and RD 3D HNNCAHA NMR experiment. 85. The method according to claim 82 further comprising: subjecting the protein sample to (i) a RD 3D If^-C^CO-HA NMR experiment to measure and connect the chemical shift values of a β-proton of amino acid residue i, 1 H ,-, a β-carbon of amino acid residue i, 13 C β ,, the α-proton of amino acid residue i, 'HY the α-carbon of amino acid residue i, 13 C α ,, and a polypeptide backbone carbonyl carbon of amino acid residue i, 13 C',- and (ii) a RD 3D HNN<CO,CA> NMR experiment to measure and connect the chemical shift values of 13 C',-, an α-carbon of amino acid residue i+1, 13 C α !+1 , a polypeptide backbone amide nitrogen of amino acid residue i+1, 15 N, +l5 and a polypeptide backbone amide proton of amino acid residue i+1, ! H N H -I; and obtaining sequential assignments by matching the chemical shift value of 13 C',- measured by said RD 3D HNN<CO,CA> NMR experiment with the chemical shift value of 13 C' / measured by said RD 3D H α β ,C α/β ,CO,HA NMR experiment. 86. The method according to claim 82 further comprising: subjecting the protein sample to a RD 3D H α β C α/β (CO)NHN NMR experiment (i) to measure and connect the chemical shift values of the α- and β-protons of amino acid residue i-1, 1 H α/β , -1 , α- and β-carbons of amino acid residue i-1, 13 C α/β 7-1 , 15 N / , and 'H* 1 ,, and (ii) to distinguish NMR signals for the chemical shift values of 1H β M , 13 C β M , 'iTYi, and 13 C α measured by said RD 3D H α/β C α/β (CO)NHN NMR experiment from NMR signals for the chemical shift values of l n i and 13 C a,i M other than 1 H α/β !-1 and 13 C α/β measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. 87. The method according to claim 82 further comprising: subjecting the protein sample to a RD 3D H α/β ,C α β ,N,HN NMR experiment to measure and connect the chemical shift values of 1H β / , 13 C β 3 1HΥ 13 C α ; , 15 N,-, and 1H N / ; and obtaining sequential assignments by matching the chemical shift values of 1H β ; , 13 C β r -, 1HΥ and 13 C α ; measured by said RD 3D H α/β ,C α β ,N,HN NMR experiment with the chemical shift values of 1 H β , -1 , 13 C β ,-. 1 , 1 H α / . 1 , and 13 C n measured by said RD 3D H,C,(C- TOCSY-CO),N,HN NMR experiment. 88. The method according to claim 82 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to measure and connect the chemical shift values of 13 C β ,-, 13 C α , 15 N,, and 'H 1 ^; and obtaining sequential assignments by matching the chemical shift values of 13 C β ; and 13 C α measured by said 3D HNNCACB NMR experiment with the chemical shift values of 13 C β and 13 C α M measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. 89. The method according to claim 82 further comprising: subjecting the protein sample to a RD two-dimensional (2D) HB,CB,(CG,CD),HD NMR experiment to measure and connect the chemical shift values of , H β ;, 13 C β ,, and a δ-proton of amino acid residue i with an aromatic side chain, 'H 8 ,-; and obtaining sequential assignments by matching the chemical shift values of 1H β ; and 13 C β , measured by said RD 2D HB, CB,(CG, CD), HD NMR experiment with the chemical shift values of 1H β and 13 C β measured by said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment, using said chemical shift values to identify amino acid residue i as having an aromatic side chain, and mapping sets of sequentially connected chemical shift values to the amino acid sequence of the polypeptide chain and locating amino acid residues with aromatic side chains along said polypeptide chain. 90. The method according to claim 82 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-COSY NMR experiment or a RD 3D H,C,C,H-TOCS Y NMR experiment to measure and connect the chemical shift values of aliphatic protons of amino acid residue i, 'H 3 ' 1 ,- and aliphatic carbons of amino acid residue i, 13 C di t ; and obtaining sequential assignments of the chemical shift values of 1H 3 ' 1 ,- and 13 C ali ,- by (i) matching the chemical shift values of 1H ali and 13 C ali measured using said RD 3D H,C,C,H-COSY NMR experiment or RD 3D H,C,C,H-TOCSY NMR experiment with the chemical shift values of 1H β ,-, 13 C β 5 1H α ; -, and 13 C\- measured by said RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment and RD 3D HNNCAHA NMR experiment, and (ii) using the chemical shift values of 1H ah / and 13 C ah ,-, to identify the type of amino acid residue i. 1 91. A method for obtaining assignments of chemical shift values of H, C and 15 N of a protein molecule comprising: providing a protein sample; and conducting four reduced dimensionality (RD) nuclear magnetic resonance (NMR) experiments on the protein sample, wherein (1) a first experiment is selected from the group consisting of a RD three-dimensional (3D) H α β C α/β (CO)NHN NMR experiment, a RD 3D HA,CA,(CO),N,HN NMR experiment, and a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment for obtaining sequential correlations of chemical shift values; (2) a second experiment is selected from the group consisting of a RD 3D HNNCAHA NMR experiment, a RD 3D H α β ,C α/β ,N,HN NMR experiment, and a RD 3D HNN<CO.CA> NMR experiment for obtaining intraresidue correlations of chemical shift values; (3) a third experiment is a RD 3D H,C,C,H-COS Y NMR experiment for obtaining assignments of sidechain chemical shift values; and (4) a fourth experiment is a RD two-dimensional (2D) HB.CB,(CG.CD),HD NMR experiment for obtaining assignments of aromatic sidechain chemical shift values. 92. The method according to claim 91 further comprising: subjecting the protein sample to a RD 2D H,C,H-COSY NMR experiment for obtaining assignments of sidechain chemical shift values. 93. The method according to claim 91 , wherein the first experiment is the RD 3D H α β C α/β (CO)NHN NMR experiment and the second experiment is the RD 3D HNNCAHA NMR experiment. 94. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D HA,CA,(CO),N,HN NMR experiment to distinguish between NMR signals for 1H α / 13 C α and 1H β / 13 C β from said RD 3D H α β C α β (CO)NHN NMR experiment. 95. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment to obtain assignments of chemical shift values of 1H a and 13 C ah . 96. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D H α/β ,C α β ,N,HN NMR experiment to obtain assignments of chemical shift values of 1H β and 13 C β . 97. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D HNN<CO,CA> NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, 13 C. 98. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D H^,C α β ,CO,HA NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, 13 C\ 99. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D HNN<CO,CA> NMR experiment and a RD 3D H^C^CO^A NMR experiment to obtain assignments of chemical shift values of 13 C. 100. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aliphatic sidechains. 101. The method according to claim 93 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of H and C of aromatic sidechains. 102. The method according to claim 93 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . 103. The method according to claim 93, wherein the first experiment is the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the second experiment is the RD 3D HNNCAHA NMR experiment. 104. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D HA,CA 5 (CO),N,HN NMR experiment to identify NMR signals for 1H 13 C α in said RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment. 105. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D H α β ,C α/β ,N,HN NMR experiment to obtain assignments of chemical shift values of 1H β and 13 C β . 106. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D HNN<CO,CA> NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, C . 107. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D H α β ,C α β ,CO,HA NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, 13 C\ 108. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D HNN<CO.CA> NMR experiment and a RD 3D H α β ,C α/β ,CO,HA NMR experiment to obtain assignments of chemical shift values of 13 C. 109. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aliphatic sidechains. 110. The method according to claim 103 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment 1 1 to obtain assignments of chemical shift values of H and C of aromatic sidechains. 111. The method according to claim 103 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . 112. The method according to claim 91, wherein the first experiment is the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the second experiment is the RD 3D H α/β ,C α β ,N,HN NMR experiment. 113. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D HA,CA,(CO),N,HN NMR experiment to identify NMR signals for 1H α and 13 C α in said RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment. 114. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D H α/β C α β (CO)NHN NMR experiment to identify NMR signals for 1 H α β and 13 C α/β in said RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment. 115. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D HNN<CO,CA> NMR experiment to 1 obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, C . • 116. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D H α/β ,C α/β ,CO,HA NMR experiment to obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, 13 C. 117. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D HNN<CO.CA> NMR experiment and a RD 3D H α β ,C α β ,CO,HA NMR experiment to obtain assignments of chemical shift values of 13 C. 118. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment 1 1^ to obtain assignments of chemical shift values of H and C of aliphatic sidechains. 119. The method according to claim 112 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of H and C of aromatic sidechains. 120. The method according to claim 112 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . 121. The method according to claim 91, wherein the first experiment is the RD 3D H,C,(C-TOCSY-CO),N,HN NMR experiment and the second experiment is the RD 3D HNN<CO.CA> NMR experiment. 122. The method according to claim 121 further comprising: subjecting the protein sample to a RD 3D HA,CA,(CO),N,HN NMR experiment to identify NMR signals for 1H α and 13 C α in said RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment. 123. The method according to claim 121 further comprising: subjecting the protein sample to a RD 3D H α/β C α β (CO)NHN NMR experiment to identify NMR signals for 1H α β and 13 C α β in said RD 3D H,C,(C-TOCSY- CO),N,HN NMR experiment. 124. The method according to claim 121 further comprising: subjecting the protein sample to a RD 3D H α β ,C α/β ,CO,HA NMR experiment o obtain assignments of chemical shift values of polypeptide backbone carbonyl carbons, 13 C\ 125. The method according to claim 121 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment to obtain assignments of chemical shift values of 1H and 13 C of aliphatic sidechains. 126. The method according to claim 121 further comprising: subjecting the protein sample to a RD 3D H,C,C,H-TOCSY NMR experiment 1 1 ^ to obtain assignments of chemical shift values of H and C of aromatic sidechains. 127. The method according to claim 121 further comprising: subjecting the protein sample to a 3D HNNCACB NMR experiment to obtain assignments of chemical shift values of 13 C β . 128. The method according to claim 91 further comprising: subjecting the protein sample to nuclear Overhauser effect spectroscopy (NOESY) to deduce the tertiary structure of the protein molecule. 129. The method according to claim 91 further comprising: subjecting the protein sample to NMR experiments that measure scalar coupling constants to deduce the tertiary structure of the protein molecule. 130. The method according to claim 91 further comprising: subjecting the protein sample to NMR experiments that measure residual dipolar coupling constants to deduce the tertiary structure of the protein molecule.

Inventors: SZYPERSKI THOMAS A, SZYPERSKI, THOMAS, A.
Applicants: UNIV NEW YORK, THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK
Application year: 2001
Main classification: G01R
IPC codes: G01R33