bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structure of a rhombohedral R6 insulin hexamer that binds phenol
Authors: Smith G. D. , Dodson G. G. 
Published: December 2004

AbstractDifferent hexameric forms of insulin have been crystallized from a variety of conditions. In the presence of 1% phenol, 1.0 M sodium chloride, and at a pH of 8.5, a rhombohedral form is produced with two monomers in the asymmetric unit, space group R3, a = 79.92 Å and c = 40.39 Å. The structure has been solved and refined, using data between 8.0 and 2.5 Å resolution, to a residual of 0.157. Each of the monomers adopts an R conformation, that is residues B1–B8 are α‐helical. As a result of the T to R transition, an elliptical cavity is created between symmetry–related monomers and is occupied by a phenol molecule. A region of density within bonding distance to one of the zinc ions has been interpreted as an additional phenol molecule.
A new constraint potential for the structure refinement of biomolecules in solution using experimental nuclear overhauser effect intensity
Authors: Stawarz Bernard , Genest Monique , Genest Daniel 
Published: December 2004

AbstractA new constraint potential is proposed for the refinement of the three‐dimensional structure of biomolecules in solution from nmr data. It is based on the nuclear Overhauser effect (NOE) intensity calculations, taking into account the spin diffusion phenomenon. For restrained energy minimization or molecular dynamics techniques, a constraint potential term expressed as a function of the negative inverse of the sixth power of the NOE intensities (NOE−1/6) is added to the classical potential energy function. The properties of this new NOE constraint potential are discussed and compared to those of a harmonic NOE intensity potential.The method integrated in the molecular modeling program GROMOS is tested on the regular α‐helical structure of a decaglycylpeptide.
Solution structures of cyclic and dicyclic analogues of growth hormone releasing factor as determined by two‐dimensional NMR and CD spectroscopies and constrained molecular dynamics
Authors: Fry David C. , Madison Vincent S. , Greeley David N. , Felix Arthur M. , Heimer Edgar P. , Frohman Lawrence , Campbell Robert M. , Mowles Thomas F. , Toome Voldemar , Wegrzynski Bogda B. 
Published: December 2004

AbstractSolution structures were determined for a linear analogue of growth hormone releasing factor (GRF), and cyclic and dicyclic analogues in which the side chains of aspartyl and lysyl residues spaced at positions i‐(i + 4) were joined to form a lactam. The four analogues were [Ala15]‐GRF‐(1–29)‐NH2 and its cyclo8–12, cyclo21–25, and dicyclo8–12;21–25 derivatives. The peptides were studied in two solvent systems: 75% methanol/25% water at pH 6.0; and 100% water at pH 3.0. CD spectroscopy was used to assess the overall α‐helical content. Nuclear magnetic resonance spectroscopy was used to determine the structures in more detail. Nearly complete proton resonance assignments were made for each of the peptides, in both solvents. Nuclear Overhauser effects were converted into distance constraints and applied in the molecular dynamics program CHARMM to evaluate the range of low‐energy structures that satisfied the nmr data. In 75% methanol, all of the peptides are comprised of a single α‐helical segment with fraying of one to three residues at each end. The linear analogue has a tendency to kink. In water, the analogues have two helical segments with flexible regions between them and at the termini of the peptides. The linear analogue is helical at residues 7–14 and 21–28. In the cyclo8–12 analogue, the N‐terminal helical region extends to include residues 7–19, while the other helical region is slightly shortened. In the cyclo21–25 analogue, the C‐terminal helical region is extended to include residues 19–28, while the N‐terminal helical region is destabilized. The dicyclic analogue has the largest N‐terminal helix, spanning residues 7–20, but its helical segment at residues 21–28 is not well ordered. All of the analogues exhibit substantial biological activity. The cyclic and dicyclic analogues show dramatically increased resistance to degradation during incubation with human plasma. The i−(i + 4) lactam, therefore, appears to be a synthetic means of stabilizing a local α‐helical conformation, which may be of general use in the design of active, stable peptides.
Molecular structure of cyclo[‐(D‐Val‐L‐Hyi‐L‐Val‐D‐Hyi)2‐] revealed by X‐ray analysis
Authors: Grochulski P. , Smith G. D. , Langs D. A. , Duax W. L. , Pletnev V. Z. , Ivanov V. T. 
Published: December 2004

AbstractThe crystal structure of a synthetic analogue of valinomycin, cyclo [‐(D‐Val‐L‐Hyi‐L‐Val‐D‐Hyi)2‐] (octa‐meso‐valinomycin) (I) (C40H68N4O12 · 1.5 · C4H8O2, Mr = 937.01 + 88.10), has been determined. Crystals grown from dioxane are monoclinic, space group P21/a, with cell parameters a = 21.487(8), b = 16.836(5), c = 16.089(4) Å, β = 111.70(4), and Z = 4. The atomic coordinates for nonhydrogen atoms were refined in the anisotropic thermal motion approximation. H atom positions were included in the structure factor calculations at their geometrically expected positions. Values of the standard and weighted R factors after refinement are 0.11 and 0.13, respectively. The conformation of the depsipeptide crystallized from dioxane is different from that crystallized from chloroform (II). The molecule adopts a rectangular shape with two type IV β–turns containing a hydrogen bond and possesses pseudorotational symmetry. The side chains are located on the molecular periphery. The orientation of the carbonyl groups of the molecule is not conducive for efficient metal‐ion coordination and in the observed conformation cannot behave as an ionophore.In the crystal the molecules form infinite chains parallel to the c axis, and are stabilized by two intermolecular hydrogen bonds that are shorter and have better geometry than the intramolecular hydrogen bonds.A ϕ/Ψ plot for dodecadepsipeptides with a (DLLD)3 sequence has well‐defined areas for Val and Hyi residues only in cases when the crystals have been grown from nonpolar or medium‐polar solvents. The Φ/Ψ plot for octadepsipeptides crystallized from chloroform (II) shows this behavior also. There also is a correlation between the polarity of the solvent from which crystals of octa‐meso‐valinomycin or valinomycin analogues with a (DLLD) sequence of configuration have been grown and the number of the intramolecular hydrogen bonds that are formed. The more polar the solvent the fewer the number of intramolecular hydrogen bonds.Empirical energy calculations on octa‐meso‐valinomycin indicate that for isolated molecules, the energy of the bracelet form (II) is 4.7 kcal/mole lower than that of the rectangular form (I).
Vibrational CD studies of interchain hydrogen‐bonded tripodal peptides
Authors: Paterlini M. Germana , Freedman Teresa B. , Nafie Laurence A. , Tor Yitzhak , Shanzer Abraham 
Published: December 2004

AbstractThe solution conformations of three trispeptides—L,L,L‐1,3,5‐C6H3[CH2NHCOCH(X)‐NHBoc]3, X = CH3 (Ala) or CH2CH (CH3)2 (Leu), and L,L,L‐N{CH2CH2NHCOCH [CH2‐CH(CH3)2]NHBoc}3—have been determined from their ir and vibrational CD (VCD) spectra in the NH stretching and carbonyl stretching regions in apolar solution. The compounds containing L‐Leu are shown to occur primarily in a propeller conformation with C3 symmetry that is stabilized by interchain hydrogen bonds. Through application of the coupled oscillator model of VCD, a right‐handed sense for the hydrogen‐bonded chains in the propeller is deduced, in agreement with previous empirical force field calculations. The spectra also provide evidence for interchain association between two chains, resulting in a C10‐ring. For chains not involved in interchain association, the spectra reveal the presence of C7‐rings within a chain. The trispeptide containing L‐Ala is found to occur primarily in a random form.
Elongational flow studies on DNA in aqueous solution and stress‐induced scission of the double helix
Authors: Atkins E. D. T. , Taylor M. A. 
Published: December 2004

AbstractElongational flow techniques are used to investigate the birefringent response and flow‐induced molecular scission of monodisperse phage‐DNA samples in aqueous solution. A 4‐roll mill apparatus was used to characterize the solutions ac low stain rates, \documentclass{article}\pagestyle{empty}\begin{document}$ \dot \varepsilon $\end{document} ≤ 300 s−1, and the opposed jets apparatus used to study fracture of the DNA molecules at strain rates up to 15 × 103 S−1. The molecular weight values were measured before and after fracture in elongational flow using the high‐resolution technique of pulsed field gel electrophoresis (PFGE). The birefringent response incorporates both rigid and flexible components. The birefringence is nonlocalized and rises gradually to a plateau value, similar to rigid‐rod behavior. In addition a certain minimum value in the strain rate is necessary, an onset value \documentclass{article}\pagestyle{empty}\begin{document}$ \dot \varepsilon $\end{document}0, before the signal appears, indicating a flexible component. This behavior is consistent with a hinged‐rod model and is similar to that observed for the protein collagen molecule at elevated temperature. We propose that this type of behavior is likely for multistrand rope‐like macromolecules where localized separation or partial untwisting of the intertwined chains occurs, creating temporary hinges, in accordance with biochemical evidence for sequence‐specific sites of flexibility. Results are presented on the entanglement effects at high concentrations. We have calculated rotational diffusion rates as a function of concentration and molecular weight. Using PFGE to measure the molecular weight profiles, our fracture studies at high strain rates demonstrate chain halving and quartering in accordance with the predictions of the thermally activated barrier to scission theory for single‐chain polymers.
The contribution of residue ion pairs to the helical stability of a model peptide
Authors: Stellwagen Earle , Park Soon‐Ho , Shalongo William , Jain Ashu 
Published: December 2004

AbstractComparative CD measurements were made on the model helical peptides acetyl‐YEAAAKEAXAKEAAAKAamide and acety1YEAAAEKAXAKEAAAKAamide in which X represents a nonaromatic nonionic residue. The former peptide contains three potential i, i + 4 complementary ion pairs at neutral pH, while the latter peptide contains one potential complementary and two potential antagonistic i, i + 4 ion pairs. The effect of pH and ionic strength on the mean residue ellipticity of these peptides was measured at 222 nm and 0°C. These measurements were analyzed assuming a common two‐state helix/ coil transition and only i, i, + 4 ion‐pair interactions. The analyses suggest that the central ion pairs do modulate helical content while the peripheral ion pairs do not, presumably due to the location of the peripheral ion pairs in the frayed ends of the helix. The complementary central ion pair stabilizes the helix by about 0.4 kcal/mole and the antagonistic central ion pair destabilizes the helix by about 0.2 kcal/mole. © 1992 John Wiley & Sons, Inc.
Combined use of homo‐ and heteronuclear coupling constants as restraints in molecular dynamics simulations
Authors: Mierke Dale F. , Kessler Horst 
Published: December 2004

AbstractA penalty function for scalar coupling constants has been applied in molecular dynamics simulations as an experimental constraint. The function is based on the difference between the coupling constant calculated from the dihedral angle and the experimentally measured coupling constant. The method is illustrated on a model cyclic pentapeptide for which 3JHN‐Hα and 3JHN‐Cβ, both about the ϕ backbone dihedral angle, have been measured. The function is efficient in producing structures consistent with the scalar couplings, but removed from the conformation observed in solution. This arises from the lack of J restraints for the ψ dihedral angle. Simulation with both nuclear Overhauser effect (NOE) and J‐coupling restraints illustrates small but significant differences from simulations using only NOEs. © 1992 John Wiley & Sons, Inc.
Molecular dynamics conformational search of six cyclic peptides used in the template assembled synthetic protein approach for protein de novo design
Authors: Floegel Rainer , Mutter Manfred 
Published: December 2004

AbstractSix cyclic peptides, designed to act as topological templates in the TASP (template assembled synthetic protein) approach in protein de novo design, were investigated employing a 100‐ps, 900‐K molecular dynamics conformational search. The peptides are composed of two Lys‐X‐Lys (X = Gly, Ala) tripeptides connected at its N‐ and C‐terminal end by a Pro‐Gly motif and a cystine bridge (I), two Pro‐Gly units (II), naphthalene derivatives (III), and tetrahydronaphthalene derivatives of different stereochemistry (IV‐VI). The molecular dynamics conformational search established that template I had β‐sheet like geometry. Templates II‐VI showed different preferential geometries, among them, e.g., distinct preferences for type V turns in Pro‐Gly containing peptides and close spatial arrangement of hydrophobic naphthalene moieties. The orientation of the lysine side chains within preferential geometries of the individual templates is analyzed and a tentative evaluation for their potential to stabilize TASP molecules of 4‐helix bundle topology is given. © 1992 John Wiley & Sons, Inc.
A molecular thermodynamic approach to predict the secondary structure of homopolypeptides in aqueous systems
Authors: Chen Chau‐Chyun , Zhu Yizu , King Jonathan A. , Evans Lawrence B. 
Published: December 2004

AbstractUnder physiological conditions, many polypeptide chains spontaneously fold into discrete and tightly packed three‐dimensional structures. The folded polypeptide chain conformation is believed to represent a minimum Gibbs energy of the system, governed by the weak interactions that operate between the amino acid residues and between the residues and the solvent.A semiempirical molecular thermodynamic model is proposed to represent the Gibbs energy of folding of aqueous homopolypeptide systems. The model takes into consideration both the entropy contribution and the enthalpy contribution of folding homopolypeptide chains in aqueous solutions. The entropy contribution is derived from the Flory‐Huggins expression for the entropy of mixing. It accounts for the entropy loss in folding a random‐coiled polypeptide chain into a specific polypeptide conformation. The enthalpy contribution is derived from a molecular segment‐based Non‐Random Two Liquid (NRTL) local composition model [H. Renon and J. M. Prausnitz (1968) AIChE J., Vol. 14, pp. 135–142; C.‐C. Chen and L. B. Evans (1986) AIChE J., Vol. 32, pp. 444–454], which takes into consideration of the residue‐residue, residue‐solvent, and solvent‐solvent binary physical interactions along with the local compositions of amino acid residues in aqueous homo‐polypeptides. The UNIFAC group contribution method [A. Fredenslund, R. L. Jones, and J. M. Prausnitz (1975) AIChE J., 21, 1086–1099; A. Fredenslund, J. Gmehling, and P. Rasmussen (1977) Vapor‐Liquid Equilibrium Using UNIFAC, Elsevier Scientific Publishing Company, Amsterdam], developed originally to estimate the excess Gibbs energy of solutions of small molecules, was used to estimate the NRTL binary interaction parameters.The model yields a hydrophobicity scale for the 20 amino acid side chains, which compares favorably with established scales [Y. Nozaki and C. Tanford (1971) Journal of Biological Chemistry, Vol. 46, pp. 2211–2217; E. B. Leodidis and T. A. Hatton (1990) Journal of Physical Chemistry, Vol. 94, pp. 6411–6420]. In addition, the model generates qualitatively correct thermodynamic constants and it accurately predicts thermodynamically favorable folding of a number of aqueous homopolypeptides from random‐coiled states into α‐helices. The model further facilitates estimation of the Zimm‐Bragg helix growth parameter s and the nucleation parameter s for amino acid residues [B. H. Zimm and J. K. Bragg (1959) Journal of Chemical Physics, Vol. 31, pp. 526–535]. The calculated values of the two parameters fall into the ranges suggested by Zimm and Bragg. © 1992 John Wiley & Sons, Inc.
Analysis of the effectiveness of proline substitutions and glycine replacements in increasing the stability of phage T4 lysozyme
Authors: Nicholson H. , Tronrud D. E. , Becktel W. J. , Matthews B. W. 
Published: December 2004

AbstractIt was previously shown that the two replacements Gly 77 ↠ Ala (G77A) and Ala 82 ↠ Pro (A82P) increase the thermostability of phage T4 lysozyme at pH 6.5. Such replacements are presumed to restrict the degrees of freedom of the unfolded protein and so decrease the entropy of unfolding [B. W. Matthews, H. Nicholson, and W. J. Becktel (1987) Proceedings of the National Academy of Science USA Vol. 84, pp. 6663–6667].To further test this approach, three additional replacements—G113A, K60P and A93P— have been constructed. On the basis of model building, each of these three replacements was judged to be less than optimal because it would tend to introduce unfavorable van der Waals contacts with neighboring parts of the protein. The presence of such contacts was verified for G113A and K60P by conformational adjustments seen in the crystal structures of these mutant proteins. In the case of G113A there are backbone conformational changes of 0.5–1.0 Å in the short α‐helix, 108–113, that includes the site of substitution. In the case of K60P the pyrrolidine ring shows evidence of strain. The thermal stability of each of the three variants at both pH 2.0 and pH 6.5 was found to be very close to that of wild‐type lysozyme. The results suggest that the procedure used to predict sites for both Xaa ↠ Pro and Gly ↠ Ala is, in principle, correct. At the same time, the increase in stability expected from substitutions of this type is modest, and can easily be offset by strain associated with introduction of the alanine or proline. This means that the criteria used to select substitutions that will increase thermostability have to be stringent at least. In the case of T4 lysozyme this severely limits the number of sites. The analysis reveals a significant discrepancy between the conformational energy surface predicted for the residue preceding a proline and the conformations observed in crystal structures. © 1992 John Wiley & Sons, Inc.
DNA torsional dynamics by multifrequency phase fluorometry
Authors: Collini Maddalena , Chirico Giuseppe , Baldini Giancarlo 
Published: December 2004

AbstractThe time decay of the fluorescence polarization anisotropy of calf thymus DNA‐ethidium complexes is obtained from measurements with sine‐modulated excitation employing the so‐called multifrequency phase fluorometry. A torsional dynamics model developed by J. M. Schurr [(1984) Chemical Physics, Vol. 84, pp. 71–96] and translated into the frequency domain is found here to describe accurately DNA‐ethidium fluorescence data collected under modulated excitation.At a low dye/DNA ratio (1 : 400) the value of the DNA torsional constant (α = 4.63 ± 0.2 10−12 dyne cm) fitting the data agrees very well with the known values of α. When the measurements are extended to a higher ethidium/DNA ratio, energy transfer effects between intercalated dyes are observed. A theoretical prediction of the donor and acceptor dye contributions to the fluorescence polarization anisotropy is made here, taking into account also dye‐dye distance distributions. © 1992 John Wiley & Sons, Inc.
The shapes of backbones of chain molecules: Three‐dimensional characterization by spherical shape maps
Authors: Arteca Gustavo A. , Mezey Paul G. 
Published: December 2004

AbstractIn this work we present a new method to characterize the shape of flexible chain molecules. The procedure associates a sphere and a spherical shape map with each given molecular backbone. Each point on the sphere is classified according to the crossing pattern obtained when the backbone is looked at along a direction defined by the center of the sphere and the chosen point. The approach is simple to implement. It consists of the following steps: (a) enclosing the backbone by a sphere, whose center is the geometrical center of the backbone; (b) projecting the backbone onto a plane tangent to the sphere at the given point; and (c) characterizing the resulting planar curve by a vector specifying the number and handedness type of the crossings. When the procedure is repeated for all points on the spherical surface, the latter is divided into regions that are equivalence classes of points, corresponding to directions from where the backbone has the same overcrossing pattern. The computation of these equivalence classes is performed automatically by the computer, by determining the boundary of the regions characterized by different crossing vectors. The characterization provided is thus direction independent since it takes into accountallpossible directions from where a backbone can be analyzed. The procedure is illustrated for a number of supersecondary protein structures and small proteins. We find that a characterization of substructures can be obtained in terms of the arrangement of the equivalence region for the viewing directions from where the backbone showsno crossings. For instance, an α‐helix is represented by a spherical map with a small “band” region of no crossings perpendicular to the helical axis. Other supersecondary structural features are described in a similar fashion. A number of refinements of the method, based on the distances between crossings, are also given for the case of irregular backbones. © 1992 John Wiley & Sons, Inc.
A study of the quadrupolar NMR splittings of 7Li+, 23Na+, and 133Cs+ counterions in macroscopically oriented DNA fibers
Authors: Schultz Johan , Nordenskiöld Lars , Rupprecht Allan 
Published: December 2004

AbstractThe hydration and temperature dependencies of the 23Na+, and 133Cs+, and 7Li+ quadrupolar splitting have been determined in hydrated, macroscopically oriented DNA fibers. At low water contents the quadrupolar splitting is found to decrease as the water content increases, regardless of counterion, while at high water contents the hydration dependence is reversed. The 23Na+ and 133Cs+ quadrupolar splittings decrease as the temperature increases, while the 7Li+ splitting shows the opposite behavior. At high water contents the 23Na+ and 133Cs+ splittings decrease, and then, after passing zero splitting, increase as the temperature increases. The interpretation of the temperature dependence is discussed in terms of a two‐site model (free and bound ions) and a three‐site model (free ions and specifically or nonspecifically bound ions). It is suggested that a three‐site model is more consistent with the data for the present system. At high water contents, the temperature dependence of the 7Li+ splitting vanishes, indicating counterion condensation. The behavior of the 7Li+ splitting is confirmed by measurements on DNA fibers in equilibrium with a C2H5OD‐D2O‐LiCl solution. The salt dependence in this system is weak. The counterion quadrupolar splitting is seen to be very sensitive to structural transitions in double‐helical DNA. © 1992 John Wiley & Sons, Inc.