bluuebunny/crossref_metadata_2025 huggingface dataset:
Local deformation studies of chain molecules: Differential conditions for changes of dihedral angles
Authors: Braun W.
Published: December 2004

New first and second‐order differential equations for changes of dihedral angles characterizing local deformations of chain molecules with fixed bond lengths and bond angles are derived. Two methods for integrating the differential relations are given. The proposed method is used to generate a path of locally deformed conformations around a β‐turn region of a small protein, bovine pancreatic trypsin inhibitor. The variable regions change their conformations by more than 3 Å root‐mean‐square distance value whereas the fixed regions stay within 0.02 Å. Possible applications of this method are in the field of computer graphics, Monte Carlo simulations, and energy minimization calculations of chain molecules.
Conformational studies of nucleic acids. V. Sequence specificities in the conformational energetics of oligonucleotides: The homo‐tetramers
Authors: Pearlman David A. , Kim Sung‐Hou
Published: December 2004

The conformational energetics of the tetranucleoside triphosphates d(ApApApA), d(GpGpGpG), d(CpCpCpC), d(TpTpTpT), ApApApA, GpGpGpG, CpCpCpC, and UpUpUpU are thoroughly examined using a classical potential energy function. The sugar modeling method and multiple correlation functions derived in previous papers of this series are utilized in these examinations. The data are analyzed and compared in terms of the energy profiles for rotation about the conformation‐determining torsion angles in the tetramers. Overall, the predictions are in reasonable qualitative agreement with the existing experimental data. It is found that the base type does not greatly affect the locations of the important minima in these profiles, but rather exerts a large influence on the relative depths of the minima and the barriers to conversion between them. Conformational sequence dependence is manifest to a greater extent by the DNA tetramers than the RNA tetramers. Of the DNA tetramers, d(CpCpCpC) appears, from the results presented herein, to have the greatest potential for polymorphism. This and other findings are analyzed in terms of the preferences of particular DNA sequences for either the A‐, B‐, or Z‐conformation.
An analysis of the 225–230‐nm CD band of elapid toxins
Authors: Hider R. C. , Drake A. F. , Tamiya N.
Published: December 2004

Spectroscopic measurements of three representative elapid toxins are presented. An analysis of the data leads to the conclusion that the 228‐nm CD band in this class of proteins originates largely in the disulfide chromophore. The intensity of this CD band is sensitive to conformational change associated with the disulfide group.
Mobility of enzymes on insoluble substrates: The β‐amylase–starch gel system
Authors: Henis Yoav I. , Yaron Tamar , Lamed Raphael , Rishpon Judith , Sahar Elhanan , Katchalski‐Katzir Ephraim
Published: December 2004

The movement of enzymes along the surfaces of biopolymers containing enzyme‐susceptible sites can be described as a lateral diffusion process characterized by an apparent diffusion coefficient [E. Katchalski‐Katzir, J. Rishpon, E. Sahar, R. Lamed, and Y. I. Henis (1985) Biopolymers 24, 257–277]. Studies on the diffusion of enzymes on biopolymer substrates can therefore provide important information on the mechanism of enzyme–biopolymer interaction. For this reason, the motion of fluorescently labeled β‐amylase [α‐D‐(1 → 4)glucan maltohydrolase; E.C. 3.2.1.2] on the surface of starch gels was studied by fluorescence photobleaching recovery. The results indicate that the motion of β‐amylase on the surface of the gel substrate occurs by both lateral diffusion along the surface (over micron distances) and exchange between bound and free enzyme molecules in the solution covering the gel, and that the two processes occur concomitantly and in a random manner. Surface diffusion also appears an important process with respect to the action of the enzyme on the substrate sites, since this component of the motion disappears upon inactivation of the enzyme, leaving only exchange to contribute to the measured motion.
A synthetic model of collagen: An experimental investigation of the triple‐helix stability
Authors: Germann H.‐P. , Heidemann E.
Published: December 2004

Variations I–XVIII of a trimerlike cross‐linked collagen model peptide were synthesized and used to investigate the cooperation of different neighboring Gly‐X‐Y tripeptides. The carboxy‐terminal decapentapeptide of the tripe‐helical part of collagen type I was chosen as the starting point of sequentially modified elongations. The transition temperatures determined by CD measurements show that the incorporation of the imino acid free tripeptides Gly‐Ala‐Ala and Gly‐Ile‐Ala results in a weakening of the triple‐helical structure. It is demonstrated that the desired thermal stability of the collagen triple helix requires the “clustered” arrangement of helix‐promoting tripeptides, especially of Gly‐Pro‐Hyp.
Effect of discrete distribution of ions on B‐ and Z‐DNA: A theoretical investigation
Authors: Devarajan Sundaram , Pattabiraman Nagarajan , Shafer Richard H.
Published: December 2004

Using an iterative approach, we have placed monovalent (“solvated”) and divalent (both solvated and “unsolvated”) ions around a 20 base pair sequence, (dC‐dG)10, in standard B and ZI conformations. The molecule with its attendant ions in the various conformations is subjected to to energy minimization using the program AMBER. In the presence of solvated cations (both monovalent as well as divalent) the B form is more stable than the Z form. However, direct binding with the unsolvated divalent cations makes the Z form more stable. Groove‐binding provides some insight into the facility with which the B to Z transition occurs with higher charged cations. In the presence of unsolvated divalent cations, the Z form binds more charges at the groove through more ligands, compared to the B form. The orientation around the CpG phosphates in the minor groove of the Z form is found ideal for ion binding. Detailed molecular models for the ion binding have been developed. In general, phosphate groups dominate the ion binding. Large perturbations are seen mostly in the angles that control the phosphate orientation.
Two‐Dimensional NMR studies of [Pro‐10] atrial natriuretic factor [7‐23]
Authors: Gampe Robert T. , Connolly Peter J. , Rockway Todd , Fesik Stephen W.
Published: December 2004

The conformational properties of an analog of atrial naturiuretic factor, [Pro‐10] ANF(7‐23), were examined in H2O, H2O/DMSO‐d6 (2/1), and DMSO‐d6 using two‐dimensional nmr techniques. The sequence differs from the native peptide by the absence of the exocyclic N‐ and C‐terminal residues, and the substitution of a proline for a glycine at position 10—a modification expected to reduce the conformational flexibility of this analog. The backbone proton nmr resonances were assigned from two‐dimensional correlated spectroscopy (2D‐COSY), relayed COSY, and 2D nuclear Overhàuser enhancement (NOE) experiments, and the solution conformation was evaluated from vicinal spin–spin coupling constants and NOE data. Despite the substitution of a proline in the sequence, [Pro‐10] ANF(7‐23) exhibits a considerable amount of flexibility in all of the solvents employed.
The combined use of NMR, distance geometry, and restrained molecular dynamics for the conformational study of a cyclic somatostatin analogue
Authors: Pepermans H. , Tourwé D. , van Binst G. , Boelens R. , Scheek R. M. , van Gunsteren W. F. , Kaptein R.
Published: December 2004

A cyclic peptide analogue of somatostatin, including the o‐aminomethylphenylacetic acid spacer, was studied by the combined use of two‐dimensional nmr spectroscopy, distance geometry, and restrained molecular dynamics. Analysis of distances determined from nuclear Overhauser effect (NOE) buildup rates revealed that these were inconsistent with a unique backbone conformation near the spacer. Assuming that the conformational heterogeneity is localized to the spacer, the NOE distances measured for the remaining part of the molecule were used to generate a large number of structures with the distance geometry algorithm, which were then refined by restrained energy minimization. Four classes of structures emerged, which together account for all observed NOEs. A representative structure of each class was further refined with the restrained molecular dynamics technique, and shown to be stable on a 20‐ps time scale. The flexibility of the spacer was examined by simulating interconversions induced by an appropriate restraining potential. As a result, the explanation for the lack of somatostatin activity of the analogue studied was reconsidered.
Molecular and crystal structures of three monothiated analogues of the terminally blocked ala‐aib‐ala sequence of peptaibol antibiotics
Authors: Bardi Renato , Piazzesi Anna Maria , Toniolo Claudio , Jensen Ole E. , Omar Rashad S. , Senning Alexander
Published: December 2004

The molecular and crystal structures of three monothiated analogues of the blocked L‐Ala‐Aib‐L‐Ala sequence of peptaibol antibiotics, t‐Boc‐L‐Ala‐Aib‐ψ(CSNH)‐L‐Ala‐OMe, Ac‐L‐Ala‐Aib‐ψ(CSNH)‐L‐Ala‐OMe, and Ac‐ψ(CSNH)‐L‐Ala‐Aib‐L‐Ala‐OMe, determined by x‐ray diffraction analyses, are reported. In all cases the peptide chain is folded with φ,ψ angles close to or slightly distorted from those expected for a type II β‐bend conformation. However, the 4 → 1 H‐bond distance falls within the accepted limits only for Ac‐L‐Ala‐Aib‐ψ(CSNH)‐L‐Ala‐OMe. The structures are compared with those already published for their two oxygenated analogues.
Mechanism of fibrin coagulation based on selective, cation‐driven, protofibril association
Authors: Marx Gerard
Published: December 2004

The cation sensitivity of linear and lateral assembly processes of thrombin‐ and reptilase‐activated fibrinogen was examined. Analytic ultracentrifugation shows that the linear assembly of fibrin oligomers (protofibrils) is neither cation dependent nor sensitive to chelating agents. Protofibrils generated with thrombin–hirudin gelate with either 1–2 mM Ca(II) or 15–100 μM Zn(II). By contrast, protofibril B, generated with reptilase–diisopropylfluorophosphonate, gelates only with Ca(II) but is insensitive to Zn(II). These results indicate that the release of fibrinopeptides A and B (FPA and FPB) expose two types of lateral binding sites that are sensitive to Ca(II) and Zn(II) respectively. Transmission electron (TEM) micrographs of negatively stained gels indicate that the linear packing of the monomers within the fibrin‐ and cation‐induced protofibrin fibers is essentially identical. Scanning electron (SEM) micrographs show that the Ca(II)‐induced protofibrin B gel is similar to fibrin. In all, it seems that branching and gelation derive from two types of cation‐sensitive, lateral associative processes. Based on these findings, a new paradigm for fibrin coagulation is proposed.
The crystal and molecular structure of the anticancer drug actinomycin D—some explanations for its unusual properties
Authors: Ginell Stephan , Lessinger Leslie , Berman Helen M.
Published: December 2004

The crystal structure of the antitumor antibiotic actinomycin D has been determined by the methods of x‐ray crystallography. There are three independent molecules in the asymmetric unit. Two of the molecules form a hydrogen‐bonded dimer. The peptides within all three molecules have very similar conformations. The greatest conformational variability in the drug molecules occurs in the torsion angles of the bonds connecting the phenoxazone ring to the peptide rings. The results of this analysis has allowed us to explain the unusual physical properties of ActD as well as to provide an explanation for the thermodynamics of its interactions with DNA.
Molecular dynamics of structural transitions and intercalation in DNA
Authors: Prabhakaran M. , Harvey Stephen C.
Published: December 2004

The large‐scale flexibility of DNA and the intercalation of actinomycin D have been studied by computer simulation using molecular dynamics. The stretching and unwinding of B and Z forms of DNA and intercalation in B‐DNA were examined through molecular dynamics simulations, and the energetics of transitions were calculated by the conformational energy minimization method. The principal results of this research are as follows: (1) A dynamic conformational pathway is presented for longitudinal stretching and unwinding of the double helix to open an intercalation site. (2) Large‐scale transitions are possible in both B and Z forms of DNA through a conformationally allowed kinetic pathway. (3) The stretching and untwisting of a 5′(CG)3′ step is energetically more favorable than for a GC step in B‐DNA. (4) The formation of an adjacent second cavity in B‐DNA requires larger energy than the formation of the first cavity, affirming the neighbor‐exclusion principle of intercalation. (5) Docking an intercalated actinomycin D in the stretched structure is shown to be geometrically and energetically feasible.
Cholesteric order in gels and films of regenerated cellulose
Authors: Ritcey Anna M. , Gray Derek G.
Published: December 2004

Congo red bound to regenerated cellulose in highly swollen gel films formed by slow precipitation from LiCl/N,N‐dimethylacetamide solution exhibits induced optical activity. The induced CD band of the dye vanishes when these films are dried under uniaxial stress, indicating that the effect is structural in origin and not simply due to association of dye with chiral centers on the cellulose chain. Cellulose was also regenerated from cellulose acetate films, cast both from isotropic and cholesteric solution, by deacetylation in aqueous ammonia. Congo red bound to cellulose regenerated from cholesteric cellulose acetate exhibits an induced CD band similar to that obtained for films precipitated from LiCl/DMAC solution. The CD spectrum of Congo red in cellulose films regenerated from isotropic cellulose acetate is featureless. These observations indicate that cellulose adopts cholesteric order on slow precipitation from solution.
Study of furanose ring flexibility in polynucleotide chains using raman spectra analysis
Authors: Pechenaya V. I. , Serikov A. A.
Published: December 2004

The bands within the range of 800–850 cm−1 of Raman spectra of polynucleotides sensitive to the change in conformation of sugar–phosphate backbone are analyzed theoretically. The bands are interpreted as the appearance of a quasi‐local deoxyribose vibrational mode whose frequency is dependent on the ring puckering. The localization region of the vibrational mode is pointed out. The theory establishes a relationship between the observed spectral intensity and the population of deoxyribose conformational states described in the framework of the pseudorotation concept. The approach developed allowed one to describe the band shapes and their temperature behavior, and to determine the pseudorotation potential of deoxyribose in the helix B‐form of A · T containing polynucleotides. Using the analysis of Raman spectra of DNA fibers in water–ethanol mixture the deoxyribose flexibility during the B‐A transition is investigated in terms of the population of conformers and effective potential. It is shown that N‐ and S‐type deoxyribose conformers are populated in the DNA B‐form (those of the S‐type are preferable), whereas N‐type conformers are primarily populated in the DNA A‐form.
Structural and energetic parameters of Ca2+ binding to peptides and proteins
Authors: Hori Kenzi , Kushick Joseph N. , Weinstein Harel
Published: December 2004

The characteristics of Ca2+‐binding sites and of the structural reorganization induced by Ca2+‐binding in storage proteins and ion carriers are being studied as models for molecular mechanisms in Ca2+ channels and in Ca2+‐dependent modulatory proteins. A first step in the study was the development of energy parameters for Ca2+ compatible with those in the CHARMM package of computer simulation software. Such parameters were obtained from an analytical fit to the potential surface for [(Ca)(OCH2)4]2+ calculated with an ab initio molecular orbital method. The resulting parametrization was tested for the hexapeptide cyclo‐(Pro‐Gly)3, and a 75 residue long calcium binding protein from bovine intestine (ICaBP). The geometrical parameters calculated for the hexapeptide and its 2:1 complex with Ca2+ were in good agreement with experimental data from crystallography and nmr. Similarly, the structure of ICaBP optimized with CHARMM using the new Ca2+ parameters showed good agreement with the x‐ray structure both in the local structures of the calcium‐binding sites and in the overall shape of the protein.
The renin–angiotensin system: An example of the study of linear peptides by x‐ray crystallography
Authors: Precigoux Gilles , Benkoulouche Mohamed , Geoffre Serge
Published: December 2004

In order to get information on the bioactive conformations of the endogenic renin substrate, a few peptide segments of angiotensinogen, along with a pepstatin analogue, were studied in the solid state by x‐ray crystallography. These results are compared with the conformations of acidic proteinase inhibitors observed at the level of the active site. Such a comparison allows us to point out some analogies and differences between the observed conformation for the peptide alone and the conformations on the active sites. The analysis of the results should be a good starting point for making hypotheses on the renin substrate bioactive conformation(s).
Nmr studies of a series of dehydrodermorphins
Authors: Castiglione‐Morelli Maria A. , Saviano Gabriella , Temussi Piero A. , Balboni Gianfranco , Salvadori Severo , Tomatis Roberto
Published: December 2004

The third and fifth aromatic residues of dermorphin, a potent μ‐opioid peptide, and of its N‐terminal fragments, from the pentapeptide to the parent heptapeptide amide, have been systematically substituted with Z‐dehydrophenylalanine (Δ‐Phe) and/or Phe to investigate the conformation–activity relationship.

The characterization in DMSO‐d6 at 500 MHz indicates that, in this solvent, all peptides adopt essentially random, extended conformations, as a consequence of the strong solvation. The chemical shift of the methyl group of D‐Ala is influenced by the precise orientation of the side chain of the third residue in a fashion that can be correlated to the μ potency, consistently with our model of μ‐receptor.

However, the complexes of the pentapeptides with 18‐crown‐6‐ether, when dissolved in chloroform, adopt ordered, folded conformations, a behavior that closely parallels the CD observations in methanol.
Regularly alternating L,D‐peptides. II. The double‐stranded right‐handed antiparallel β‐helix in the structure of t‐Boc‐(L‐Phe‐D‐Phe)4‐OMe
Authors: Di Blasio Benedetto , Benedetti Ettore , Pavone Vincenzo , Pedone Carlo , Gerber Cristoph , Lorenzi Gian Paolo
Published: December 2004

The crystal structure of Boc‐(L‐Phe‐D‐Phe)4‐OMe has been determined by x‐ray diffraction analysis. The peptide crystallizes in the triclinic system, space group P1 with a = 15.290 Å, b = 15.163 Å, c = 19.789 Å, α = 102.49°, β = 96.59°, γ = 74.22°, and Z = 2. The structure has been solved by coupling of the molecular replacement technique and expansion by tangent formula refinement of the set of known phases. Several cycles of Fourier calculations and least‐squares refinement led to the location of 194 atoms of the two independent octapeptide chains and few molecules of cocrystallized solvent (chloroform, water, and methanol). The isotropic refinement converged to R = 0.13 for the 3077 “observed” reflections.

The two independent octapeptide molecule form a dimer in the solid state: the two chains are associated by interstrand hydrogen bonds (12 of the the type NH ⃛OC) with the formation of a double‐stranded antiparallel right‐handed ↑↓ β5.6‐helix. These double helices can be represented as a cylinder with a hydrophilic inner core represented by the peptide units and an hydrophobic exterior constituted by the aromatic moieties. The dimensions of the cylinder are equal to those observed for Boc‐(L‐Val‐D‐Val)4‐OMe. In the solid state the dimers pack with each other in an hexagonal fashion with the formation of layers; between the layers, solvent molecules fill empty spaces.
Interactive nmr and computer simulation studies of lanthionine‐ring structures
Authors: Palmer D. E. , Mierke D. F. , Pattaroni C. , Goodman M. , Wakamiya T. , Fukase K. , Kitazawa M. , Fujita H. , Shiba T.
Published: December 2004

We report progress in elucidating the structure of nisin, a naturally occurring peptide antibiotic. Nisin contains five rings constrained by lanthionine or methyllanthionine bridges, as well as α,β‐unsaturated amino acids. We have determined conformations for two model compounds of ring A and a derivative of ring B through interactive nmr and computer simulation studies. High‐resolution nmr techniques provides structural information, which was further refined through molecular dynamics simulations. These methods are being applied to the remaining constrained fragments of the molecule. This conformational information will be employed in an aufbau approach to determining the structure of the entire molecule.
Direct examination of chemical kinetic laws by visual imagery. IV. Association processes between antigen‐ and fragmented antibody carrying fluorescent latex particles
Authors: Kitano Hiromi , Yan Changhong , Maeda Yasushi , Ise Norio
Published: December 2004

The binary association process was further examined by direct visual observation using a fluorescence microscope connected to an image‐processing system and by a spectrophotometric method. In the present paper, we used human serum albumin (HSA)‐ and fragmented anti‐HSA antibody‐carrying fluorescent latex particles in order to attain higher sensitivities and exclude complexities that might be caused by dissociation of the association product. The rate constant of the binary association process was estimated to be 6.0 × 108M−1s−1 at 30°C and pH 7.6. The activation parameters of the association process were evaluated. The effects of pH and viscosity of the suspension on the association process were also examined.
Hydration of B‐DNA: Comparison between the water network around poly(dG) · poly(dC) and poly(dG‐dC) · poly(dG‐dC) on the basis of Monte Carlo computations
Authors: Eisenhaber F. , Tumanyan V. G. , Eisenmenger F. , Gunia W.
Published: December 2004

A computational method is elaborated for studying the water environment around regular polynucleotide duplexes; it allows rigorous structural information on the hydration shell of DNA to be obtained. The crucial aspect of this Monte Carlo simulation is the use of periodical boundary conditions. The output data consists of local maxima of water density in the space near the DNA molecule and the properties of one‐ and two‐membered water bridges as function of pairs of polar groups of DNA.

In the present paper the results for poly(dG) · poly(dC) and poly(dG‐dC) · poly(dG‐dC) are presented. The differences in their hydration shells are of a purely structural nature and are caused by the symmetry of the polar groups of the polymers under study, the symmetry being reflected by the hydration shell.

The homopolymer duplex hydration shell mirrors the mononucleotide repeat. The water molecules contacting the polynucleotide in the minor groove are located nearly in the plane midway between the planes of successive base pairs. One water molecule per base pair forms a water bridge facing two polar groups of bases from adjacent base pairs and on different strands making a “spine”‐like structure. In contrast, the major groove hydration is stabilized exclusively by two‐membered water bridges; the water molecules deepest in the groove are concentrated near the plane of the corresponding base pair.

The alternating polymer is characterized by a marked dyad symmetry of the hydration shell corresponding to the axis between two successive base pairs. The minor groove hydration of the dCpdG step resembles the characteristic features of the homopolymer, but the bridge between the O2 oxygens of the other base‐stacking type is formed by two water molecules. The major groove hydration is characterized by high probability of one‐membered water bridges and by localization of a water molecule on the dyad axis of the dGpdC step.

The found structural elements are discussed as reasonable invariants of a dynamic hydration shell.
Flexibility of smooth and skletal tropomyosins
Authors: Swenson Charles A. , Stellwagen Nancy C.
Published: December 2004

The rotational relaxation times of nonpolymerizable skeletal and smooth muscle tropomyosin were measured by analysis of the decay of the zero‐field birefringence at different temperatures and salt concentrations. Skeletal tropomyosin in solution is equally well modeled as a rigid rod or as a semiflexible rod with a persistence length of 150 nm. Smooth muscle tropomyosin does not fit the rigid rod model but is well approximated by a semiflexible rod model with a persistence length of 55 nm. The results indicate that smooth muscle tropomyosin is either a more flexible molecule than skeletal muscle tropomyosin or is a curved structure with an end‐to‐end length shorter than the coiled‐coil contour length. Smooth muscle tropomyosin controls the actomyosin ATPase differently from skeletal muscle tropomyosin and it had been suggested that the reason is because it is more rigid; clearly, another explanation must be sought.
The electrostatic potential of B‐DNA
Authors: Jayaram B. , Sharp Kim A. , Honig Barry
Published: December 2004

Electrostatic potentials around DNA are obtained by solving the nonlinear Poisson‐Boltzmann (PB) equation. The detailed charge distribution of the DNA and the different polarizabilities of the macromolecule and solvent are included explicitly in the calculations. The PB equation is solved using extensions of a finite difference approach applied previously to proteins. Electrical potentials and ion concentrations are compared to those obtained with simpler models. It is found that the shape of the dielectric boundary between the macromolecule and solvent has significant effects on the calculated potentials near the surface, particularly in the grooves. Sequence‐specific patterns are found, the most surprising result being the existence of positive regions of potential near the bases in both the major and minor grooves. The effect of solvent and ionic atmosphere screening of phosphate‐phosphate repulsions is studied, and an effective dielectric function, appropriate for molecular mechanics simulations, is derived.
Role of water molecules in the crystal structure of gly‐L‐ala‐L‐phe: A possible sequence preference for nucleation of α‐helix?
Authors: Ramasubbu N. , Parthasarathy R.
Published: December 2004

The synthetic peptide Gly‐L‐Ala‐L‐Phe (C14H19N3O4 · 2H2O; GAF) crystallizes in the monoclinic space group P21, with a = 5.879(1), b = 7.966(1), c = 17.754(2) Å, β = 95.14(2)°, Dx = 1.321 g cm−3, and Z = 2. The crystal structure was solved by direct methods using the program SHELXS‐86 and refined to an R value of 0.031 for 1425 reflections (> 3σ). The tripeptide exists as a zwitterion in the crystal and assumes a near α‐helical backbone conformation with the following torsion angles: ψ1 = −147.8°; ϕ2, ψ2 = −71.2°, −33.4°; ϕ3 ψ3 = −78.3°, −43.3°. In this structure, one water molecule bridges the COO− and NH3+ terminii to complete a turn of an α‐helix and another water molecule participates in head‐to‐tail intermolecular hydrogen bonding, so that the end result is a column of molecules that looks like an α‐helix. Thus, the two water molecules of crystallization play a major role in stabilizing the near α‐helical conformation of each tripeptide molecule and in elongating the helix throughout the crystal. An analysis of all protein sequences around regions containing a GAF fragment by Chou‐Fasman's secondary structure prediction method showed that those regions are likely to assume an α‐helical conformation with twice the probability they are likely to adopt a β‐sheet conformation. It is conceivable that a GAF fragment may be a good part of the nucleation site for forming α‐helical fragments in a polypeptide, with the aqueous medium playing a crucial role in maintaining such transient species.
Crystal structure and molecular conformation of the peptide N‐Boc‐L‐gly‐dehydro‐Phe‐NHCH3
Authors: Singh T. P. , Narula Punit , Chauhan V. S. , Kaur Paramjeet
Published: December 2004

The peptide N‐Boc‐L‐Gly‐dehydro‐Phe‐NHCH3 was synthesized by the combination of N‐Boc‐L‐Gly‐dehydro‐Phe azlactone and methylamine. The peptide crystallizes in orthorhombic space group P212121 with a = 5.679(2) Å, b = 16.423(9) Å, c = 19.198(10) Å, V = 1791(2) Å3, Z = 4, dm = 1.212(5) Mg m−3, dc = 1.237(1) Mg m−3. The structure was determined by direct methods using SHELXS 86. The structure was refined by full‐matrix least squares procedure to an R value of 0.049 for 1509 observed reflections. The molecular dimensions are, in general, in good agreement with the standard values. The bond angle Cα–Cβ–Cγ in the dehydro‐Phe residue is 133.6(5)°. The peptide backbone torsion angles are θ1 = −171.4(4)°, ω0 = 178.2(4)°, ϕ1 = −57.2(6)°, ψ1 = 141.2(4)°, ω1 = −174.4(4)°, ϕ2 = 71.5(6)°, ψ2 = 7.2(6)°, and ω2 = −179.8(5)°. These values show that the backbone adopts the β‐bend type II conformation. The Boc group has a trans‐trans conformation. The side‐chain torsion angles in dehydro‐Phe are χ2 = 1.6(9)°, χ = 0.5(9)°, and χ = 179.8(6)°. The plane of C–C–C is rotated with respect to the plane of the phenyl ring at 0.5(6)°, which indicates that the atoms of the side chain of the dehydro‐Phe residue are essentially coplanar. As a result of the β‐bend in the structure, an intramolecular hydrogen bond is formed between the oxygen of the ith residue and the NH of the (i + 3)th residue at a distance of 2.940(5) Å. The crystal structure is stabilized by a network of hydrogen bonds and van der Waals interactions.
Solvation thermodynamics of biopolymers. II. Correlations between functional groups
Authors: Ben‐Naim A. , Ting K.‐L. , Jernigan R. L.
Published: December 2004

The extent of correlations between functional groups that can form hydrogen bonds with solvent molecules has been estimated. From the observed distance distribution of functional groups on the surfaces of several proteins, and from the extent of correlation between pairs of such functional grups, we conclude that the assumption of independence of functional groups made in part I is probably a good approximation. The reason is that even when correlations exist there is, on average, cancellation of the positive and negative correlations. The relevance of hydrogen bonding with the solvent to the relative stability of different conformers of biopolymers is also indicated.
Relaxation effects in the gel electrophoresis of DNA in intermittent fields
Authors: Jamil Tahir , Frisch Harry L. , Lerman L. S.
Published: December 2004

The electrophoretic mobility of restriction fragments of lambda DNA in agarose gels declines if the field is intermittent rather than continuous, with a greater effect on the longer fragments. The changes are compatible with the assumption of two exponential relaxation processes for field‐dependent configurational changes, one when the field is turned on and another when it terminates. The length dependence at the extrapolated limit of mobility for short pulses with long intervals corresponds closely to the simple inverse proportionality to length expected from theoretical considerations when the molecular configuration is not affected by the electric field. Simple intermittent fields would allow separation of longer molecules than can ordinarily be resolved. The relaxation times for both the change in conformation imposed by the field and the return to field‐free conformation vary as approximately the second power of the length of the molecule, independent of the salt concentration or field strength and varying only slightly with gel density. These relations are not in good agreement with properties expected from reptation theory, and they suggest that a different mechanism must be invoked for the electrophoretic migration of long DNA molecules at ordinary values of field strength.
Conformational transitions of leucine‐containing isomeric sequential basic polytripeptides
Authors: Štokrová Štěpánka , Bohdanecký Miloslav , Bláha Karel , Šponar Jaroslav
Published: December 2004

Conformational transitions of basic sequential polytripeptides (Lys‐Ala‐Leu)n, (Arg‐Ala‐Ala)n, (Arg‐Leu‐Ala)n, and (Arg‐Ala‐Leu)n, induced by elevated salt concentrations and/or temperatures in aqueous solutions, were investigated by CD, sedimentation equilibrium, and viscometry. The behavior of (Lys‐Ala‐Leu)n was compared with that of the sequential isomer (Lys‐Leu‐Ala)n, studied previously. It was found that both polypeptides are highly helical with a tendency to aggregate in high salt solutions. Although the hydrophobic interactions between Lys and Leu residues play an important role in both cases, the final effect on helix stabilization and aggregation is different. The Arg‐containing polypeptides were found to assume the α‐helical conformation. Compared to the Lys‐containing polypeptides (Lys‐Ala‐Leu)n and (Lys‐Leu‐Ala)n, a very low tendency to aggregate was observed.
Solution conformation of the actinomycin D related pentapeptide lactone using nmr and molecular modeling
Authors: Mauger Anthony B. , Gallagher Kathleen S. , Silverton James V. , Ferretti James A.
Published: December 2004

A detailed description of the two observed solution conformations of the pentapeptide lactone fragment of actinomycin D is presented using the distance constraints obtained from two‐dimensional nuclear Overhauser enchancement spectra in combination with minimum energy calculations. Low energy conformational states that are compatible with the experimental distances are found for each of the two conformers. For one conformer, an all trans peptide bond conformation is found with no intramolecular hydrogen bonds. For the other conformer, the D‐Val–Pro and Pro–Sar peptide bonds were cis; this solution conformation is the same as that found in both the crystal structure of the pentapeptide lactone as well as of the native actinomycin D itself. These results are discussed in terms of the combined influence of conformation and the effects of mutual intramolecular association of the pentapeptide lactone moieties in native actinomycin D on its cytotoxic activity.
The concentration dependence of the diffusion coefficient for bovine pancreatic trypsin inhibitor: A dynamic light scattering study of a small protein
Authors: Gallagher Warren H. , Woodward Clare K.
Published: December 2004

This paper reports the use of dynamic light scattering to investigate the concentration dependence of the diffusion coefficient for bovine pancreatic trypsin inhibitor (BPTI). BPTI is a small molecular weight protein (6511 Da) that has been the subject of numerous experimental studies. In addition to addressing questions that remain in the literature concerning the aggregation behavior of BPTI, we show that dynamic light scattering can be practically applied to proteins as small as BPTI, and that it can provide a useful means of parameterizing the solution behavior for proteins. We obtained values for the apparent diffusion coefficient of BPTI as a function of concentration over a range of pH values from 2.59 to 9.92 at an ionic strength of 0.3M, and over a range of ionic strength values from 0.1 to 0.5M at a pH of 7.0. The concentration dependence is linear for nearly all the conditions examined, even up to concentrations as high as 65 mg/mL. The average diffusion coefficient obtained at infinite dilution is 14.4 ± 0.2 × 10−7 cm2/s. This value agrees with that expected for a BPTI monomer hydrated with less than a monolayer of water. We used the theories of Felderhof, of Batchelor, and of Phillies, along with the DLVO theory to interpret the concentration dependence of the apparent diffusion coefficient. The variations observed with pH and ionic strength can be primarily attributed to screened coulombic interactions. In addition, there is an attractive interaction that is slightly stronger than the repulsive coulombic one, and that is essentially independent of pH and ionic strength. The attractive interactions appear to arise from nonspecific van der Waals interactions and do not lead to the formation of stable aggregates of BPTI.
A rigorous mathematical treatment for the excluded volume effect in monte carlo simulations of polymeric chains
Authors: Yeramian E. , Schaeffer F. , Caudron B. , Claverie P. , Buc H.
Published: December 2004

In Monte Carlo simulations of polymeric chains, the chains, the chains are most often represented as spheres, or cylinders with flat ends. In this methodological paper, we adopt a representation of the chains as spherocylinders (continuous cylinders ending in semispheres). With such a representation the testing for chain overlap, which is the crucial step for the incluson of the excluded volume effect in the simulations, can be defined in a rigorous geometrical framework. The treatment we then derive fulfills the following features:

—it allows a very simple, automatic, and exhaustive calsificatim of all the possible configurations;

—it provides a physical representation for steric hindrance effects more natural than the flat‐ended cylinders. Notably, this representation avoids the introduction of artificial anisotropies in the treatments.

This spherocylindrical representation is also well suited for several types of calculations that can be involved in elaborate Monte Carlo simulations.
Superoxide dismutase: Fluctuations in the structure and solvation of the active site channel studied by molecular dynamics simulation
Authors: Shen Jian , Subramaniam Shankar , Wong Chung F. , Mccammon J. Andrew
Published: December 2004

The molecular dynamics (MD) simulation of superoxide dismutase (SOD) in water is carried out for a total of 23 ps. The simulation system is a 26 Å sphere centered at the active site of SOD, including 1602 atoms from SOD and 1761 water molecules. There is no gross deviation from the x‐ray structure for the average MD structure. The structure and potential fluctuations around the active site are examined. The results provide new insight to the interactions between SOD and its substrate superoxide.
Anisotropy of the fluorescence from the monomer, five oligomers, and a polymer of epicatechin
Authors: Cho Donghwan , Mattice Wayne L. , Porter Lawrence J.
Published: December 2004

The steady‐state fluorescence anisotropy r has been measured at 25°C for dilute solutions of epicatechin units connected by interflavan bonds with 4β → 8 stereochemistry. The molecules studied are monodisperse oligomers from the monomer through the hexamer, and a polydisperse sample with a number‐average degree of polymerization xn of 10. The hexamer and smaller oligomers have been removed from the polydisperse sample. All samples have a very small value of r in 1,4‐dioxane and in methanol. Higher values of r are seen in ethylene glycol and in glycerol. In the latter two solvents, the monomer has significantly higher r than any species with xn > 1. This observation is interpreted as evidence for the presence of excitation migration from one monomer to another in the dimer and species of higher xn.
Syntehsis and structural stability of helichrome as an artificial hemeproteins
Authors: Sasaki Tomikazu , Kaiser Emil Thomas
Published: December 2004

A detailed procedure is described for the syntehsis of helichrome, which is the first successful example of polypeptide‐based artificial hemeprotein. The segment synthesis‐condensation approach used for the assembly of small proteins has proven to be extremely useful for protein mimetics as well. The final deprotection was performed using the TNSOTf‐thioanisole method instead of the less‐convenient hydrogen fluoride method. The unfolding transition of the α‐helical conformation of helichrome induced by guanidine hydrochloride was studied to understand the stability and dynamics of the folded structure. The resulting parameters (C0.5 = 5.2M and ΔGH2O = −4.4 kcal mol−1) characterizing helichrome denaturation were comparable to that of native globular proteins.
Z‐RNA: The solution NMR structure of r(CGCGCG)
Authors: Davis Peter W. , Adamiak Ryszard W. , Tinoco Ignacio
Published: December 2004

Left‐handed double‐helical Z‐RNA has been studied using the ribohexanucleotide pentaphosphate r(CpGpCpGpCpG). One‐dimensional proton nmr experiments were used to probe the structural details of the left‐handed helix in concentrated sodium perchlorate solution. In 1M NaClO4 the RNA adopts the normal A‐form double helix, and in 6M NaClO4 it is nearly all in the Z form. In 4M NaClO4 it exists as nearly equal parts of A form and Z form. Resonances corresponding to both A and Z form appear in the nmr spectrum, indicating that the duplex exchanges slowly between forms. Spin–spin coupling constants between protons in the ribose rings were used to determine the sugar‐pucker conformations of the individual nucleotides. Quantitative nuclear Overhauser experiments were used to determine proton–proton distances within the nucleoside, and from these distances values for the glycosidic torsion angle were determined. The results show that the cytidines adopt C2′,‐endo sugar puckers (S type) with pseudo‐rotation phase values (P) of ∼ 165°. The bases are in the anti conformation, with χ values of ∼ − 140°. The internal guanosines adopt C3′,‐endo sugar puckers (N type) with P ∼ 18°, while the 3′‐terminal guanosine ribose exists in an equilibrium between S‐ and N‐type conformations. All three guanosine bases adopt the syn conformation, with χ ∼ 70°. The results indicate that the solution structure of Z‐RNA is very similar to that of Z‐DNA.
Conformational analysis of the immunodominant epitopes of the circumsporozoite protein of Plasmodium falciparum and knowlesi
Authors: Fasman Gerald D. , Park Kyusung , Schlesinger David H.
Published: December 2004

All of the coat proteins of the sporozoite and merozoite stages of Plasmodium, determined to date, contain tandem repeats and most of these contain at least one proline residue. These tandemly repeated segments of the circumsporozite (CS) proteins of P. falciparum and P. knowlesi have been shown to constitute an immunodominant epitope. Antibodies to these peptide segments have been shown to be protective and cause the shedding of the CS protein, known as the CSP reaction. In this study, four synthetic peptides were prepared by solid‐phase peptide synthesis. The first peptide corresponds to the tetrapeptide tandem repeat in the CS protein of P. falciparum, repeated eight times, (NANP)8. The second peptide is an analogue of the first in which glycine is substituted for proline, (NANG)8. The third peptide corresponds to the tandem repeat of P. knowlesi, PK(1–24), which is repeated twice (QAQGDGANAGQP)2. The fourth peptide is a tetrapeptide repeat, corresponding to the C‐terminal tetrapeptide of PK(1–24) and is repeated eight times, (AGQP)8. It is shown by CD measurements that the presence of proline in these repeats induces an increase in β‐sheet (β‐turn) content in the (NANP)8 peptide relative to the repeat of (NANG)8 and PK(1–24) peptide in aqueous media. The (AGQP)8 peptide has the highest β‐sheet (β‐turn) content in the synthetic peptides. It is concluded that this increase in defined structure correlates well with and hence may contribute to the increased antigenicity in these repeats.
The most highly amphiphilic α‐helices include two amino acid segments in human immunodeficiency virus glycoprotein 41
Authors: Eisenberg David , Wesson Morgan
Published: December 2004

A search for highly amphiphilic α‐helices has been made in a data base of protein sequences, using the helical hydrophobic moment as a criterion of amphiphilicity. The protein segments of largest hydrophobic moment have been analyzed. For the segments whose structures are known, they are in fact α‐helices. Two of the segments having very large hydrophobic moments are from the smaller C‐terminal portion of the human immunodeficiency virus (HIV) envelope glycoprotein gp41. Also, among segments having large hydrophobic moments, but not among the most extreme, are lytic peptides such as melittin. Melittin seeks surfaces between polar and apolar phases, including the membrane–water interface. It is conceivable that the gp41 segments of extreme hydrophobic moment may participate in one of the membrane‐related functions of the HIV virus.
A · U and G · C base pairs in synthetic RNAS have characteristic vacuum UV CD bands
Authors: Johnson Kenneth H. , Gary Donald M. , Morris Patricia A. , Sutherland John C.
Published: December 2004

The vacuum UV CD spectra of GpC, GpC, GpG, poly[r(A)], poly[r(C)], poly[r(U)], poly[r(A‐U)], poly[r(G) · r(C)], poly[r(A) · r(U)], and poly[r(A‐U) · r(A‐U)] were measured down to at least 174 nm. These spectra, together with the published spectra of poly[r(G‐C) · r(G‐C)], CMP, and GMP, were sufficient to estimate the CD changes upon base pairing for four double‐stranded RNAs.

The vacuum UV CD bands of poly[r(A)], poly[r(C)], and the dinucleotides GpC and CpG were temperature dependent, suggesting that they were due to intrastrand base stacking. The dinucleotide sequence isomers GpC and CpG had very different vacuum UV CD bands, indicating that the sequence can play a role in the vacuum UV CD of single‐straded RNA.

The vacuum UV CD bands of the double‐stranded (G · C)‐containing RNAs, poly[r(G) · r(C)] and poly[r(G‐C) · r(G‐C)], were larger than the measured or estimated vacuum UV CD bands of their constituent single‐stranded RNAs and were similar in having an exceptionally large positive band at about 185 nm and negative bands near 176 and 209 nm. These similarities were enhanced in difference‐CD spectra, obtained by subtracting the CD spectra of the single strands from the CD spectra of the corresponding double strands. The (A · U)‐containing double‐stranded RNAs poly[r(A) · r(U)] and poly[r(A‐U) · r(A‐U)] were similar only in that their vacuum UV CD spectra had a large positive band at 177 nm. The spectrum of poly[r(A) · r(U)] had a shoulder at 188 nm and a negative band at 206 nm, whereas the specturm of poly[r(A‐U) · r(A‐U)] had a positive band at 201 nm. On the other hand, difference spectra of both of the (A · U)‐containing polymers had positive bands at about 177 and 201 nm. Thus, the difference‐CD spectra revealed CD bands characteristic of A · U and G · C base pairing. A · U base pairs induced two positive bands at about 177 and 201 nm, whereas G · C base pair induced a large positive band at 186 nm and negative bands at about 175 and 202 nm.
Small‐angle neutron scattering study of the structure of protein / detergent complexes
Authors: Guo X. H. , Zhao N. M. , Chen S. H. , Teixeira J.
Published: December 2004

Small‐angle neutron scattering (SANS) was used to study the structure of protein/sodium dodecylsulfate complexes. Two water soluble proteins, bovine serum albumin (BSA) and ovalbumin (OVA), were used. The protein concentration was kept constant at 1 wt %, and protein/detergent wt ratio varied between 1/1, 1/1.5, 1/2 and 1/3. Absolute intensities of SANS distributions were analyzed by a fractal model. Analyses of large Q portions of SANS distributions established that sodium dodecylsulfate (SDS) molecules bound to a protein/SDS complex form micelle‐like clusters. On the other hand, analyses of small Q portions of SANS distributions clearly showed that the arrangement of micelle‐like clusters resembles a fractal packing of spheres. We showed that a protein/SDS complex can be characterized by four parameters extracted from the scattering experiment, namely, the average micelle size and its aggregation number, the fractal dimension characterizing the conformation of the micellar chains, the correlation length giving the extent of the unfolded polypeptide chains, and the numbers of micelle‐like clusters in the complex.