bluuebunny/crossref_metadata_2025 huggingface dataset:
Motions of an α‐helical polypeptide: Comparison of molecular and harmonic dynamics
Authors: Perahia D. , Levy R. M. , Karplus M.
Published: December 2004

Molecular and harmonic dynamics simulations have been performed for a decaglycine α‐helix. The extent of anharmonicity for various observables is studied by a direct comparison of the two types of simulations, at temperatures ranging from 5 to 300 K. The fluctuations of the cartesian, internal and normal mode coordinates, and their time dependence, are analyzed. The heat capacity of the α‐helix is evaluated both from the temperature response of the system to an energy perturbation and from the fluctuations in the temperature of the system. It is shown that the anharmonicity depends on the kind of observable. The root mean square atomic fluctuations have significant anharmonic components at temperatures above 100 K. In contrast, the dihedral angle fluctuations are much closer to being harmonic at all the temperatures considered. The analysis of potentials of mean force experienced by individual atoms shows that atomic displacements have approximately Gaussian distributions from 50 to 300 K, with different force constants at each temperature (quasi‐harmonic model). At 300 K, the force constants obtained by molecular dynamics are significantly lower than in the harmonic case. The time dependence of the projection of the molecular dynamics displacements on the normal mode coordinates shows that mode mixing is important above 100 K. The motions of the helix associated with the low‐frequency normal modes are described and illustrated.
Study of large DNA fragments in agarose gels by transient electric birefringence
Authors: Chu Benjamin , Wang Zhulun , Xu Renliang , Lalande Marc
Published: December 2004

The pulsed‐field gel electrophoresis (PFG) is a newly developing technique used in the fractionation of large DNA fragments. Advances in PFG demand a better understanding in the corresponding mechanisms of DNA dynamics in the gel network. Detailed experiments are needed to verify and to extend existing theoretical predictions as well as to find optimum conditions for effecient separation of large DNA fragments. In the present study, deformation of large DNA fragments (40 ∼ 70 kilobase pairs) imbedded in agarose gels were investigated by using the transient electric birefringence (TEB) technique under both singular polarity and bipolarity electric pulses at low applied electric field strengths (E ≤ 5 V/cm). The steady‐state optical retardation (δs) of DNA molecules is linearly proportional to E2. At a given E, the amplitude of optical retardation [δ(t)] increases monotonically with the pulse width (PW) and then reaches a plateau value [δ(t = 0) = δs] where t = 0 denotes the time when the applied field is turned off or reversed. The field‐free decay time (τ ∼ a few minutes) is several orders of magnitudes slower than that from previous TEB observations using high electric field strengths (E ∼ kV/cm) and short pulse widths (PW ∼ ms). The degree of deformation (stretching and orientation) and the time of restoration to the equilibrium conformation of overall DNA chains have been related to δ and τ. In field inversion measurements, exponentially rising and linearly falling of birefringence signals in the presence of forward/inverse applied fields were observed. The rising and falling of birefringence signals were reproducible under a sequence of alternating pulses. Comparison of our results with literature findings and discussions with theories are presented.
Induction of CD in some anionic dyes by cationic chitosan
Authors: Pal Medini Kanta , Pal Prasun Kumar
Published: December 2004

Chitosan can be converted into a polycation by dissolving it in an acid, and this polycation (I) induces blue‐shifted metachromasia in suitable anionic dyes, C.I. acid red 88 and C.I. acid orange 7, after reacting with the dyes with 1 : 1 stoichiometry (P/D). Both these dye–polymer systems exhibit strong biphasic CD in the visible range. Biphasic CD, as well as blue‐shifted metachromasia, indicates strong dye–dye interactions in these systems. Monophasic CD are observed only in conditions where metachromasia is partially disrupted due to poor dye–dye interactions.

The 21‐helical conformation, as confirmed for the present polymer chitin as well as for neutral chitosan, seems to be inadequate in explaining the observed results with (I).
Molecular dynamics simulations and the conformational mobility of blood group oligosaccharides
Authors: Yan Zhen‐Yi , Bush C. Allen
Published: December 2004

Molecular dynamics simulations were carried out without explicit consideration of solvent to explore the conformational mobility of blood group A and H oligosaccharides. The potential energy force field of Rasmussen and co‐workers was used with the CHARMM program on a number of disaccharide and trisaccharide models composed of fucose, galactose, glucose, N‐acetyl glucosamine, and N‐acetyl galactosamine chosen to represent various fragments of blood group oligosaccharides. In agreement with results of earlier studies, stable chair conformations were found for each pyranoside from which no transitions were detected in simulations as long as 800 ps. Exocyclic dihedral angles, including that of C5—C6, generally show numerous transitions on a time scale of approximately 5–30 ps. The dihedral angles of some but not all glycosidic linkages of blood group oligosaccharides show transitions on the time scale of 30–50 ps, implying that the extent of internal motion in blood group oligosaccharides depends strongly on linkage stereochemistry. For certain blood group A and H oligosaccharides that show limited internal motion in these simulations, we argue that the calculations are consistent with our previous analysis of 1H nuclear Overhauser enhancement (NOE) data that imply single conformations over a wide range of temperature and solvent conditions. While the trajectories are consistent with 13C T1 values that have been interpreted as indicating rigid conformations, measurements of 13C‐NOE and T1 as a function of magnetic field strength are proposed as an improved method for experimental detection of the internal motion that is suggested for certain oligosaccharides in these simulations. The results of these simulations differ substantially from those of peptides of a similar molecular weight in that the oligosaccharides show much less internal motion.
Reversibility of acid denaturation of recombinant interferon‐γ
Authors: Arakawa Tsutomu , Hsu Yeuh‐Rong , Narachi Michael A. , Herrera Charles , Rohde Michael F. , Hennigan Paul
Published: December 2004

It has been shown that interferon‐γ (IFN‐γ) loses activity after acid treatment and this property can be used to distinguish it from other types of interferons. Therefore, reversibility of acid denaturation of IFN‐γ was examined using the reconbinant human protein. The fluorescence spectra showed that conformation of the protein is similar before and after acid treatment, suggesting reversibility of the acid denaturation. The antiviral activity of the protein was also identical in the same treatment. However, the antiviral activity was significantly reduced when it was determined by directly diluting the acidic samples into the assay medium containing high salts and serum proteins. Similar results were obtained with the recombinant murine IFN‐γ. This observation demonstrates that acid denaturation of the IFN‐γ is dependent on the way the protein is renatured, and hence that the difference in response to acid treatment between IFN‐γ and other interferons is quantitative rather than qualitative.
ΔV̄0 of the Na+‐induced B‐Z transition of poly[d(G‐C)] is positive
Authors: Macgregor Robert B. , Chen Marilyn Y.
Published: December 2004

The equilibrium between the right‐ and left‐handed conformations of poly[d(G‐C)] in aqueous NaCl shifts towards the right‐handed (B) form with increasing pressure. The optical density at 290 and 260 nm was determined at 50 and 180 MPa for solutions in which approximately equal amounts of the two conformations were present at 0.1 MPa (atmospheric pressure). Interpretation of the observed changes in terms of a two‐state unimolecular reaction mechanism results in an average molar reaction volume (ΔV̄0) equal to 26 cm3 mol−1 at 22°C; that is, the partial molar volume of B form poly [d(G‐C)] is smaller than that of the left‐handed (Z) form. Based upon the thermodynamics of ion‐pair formation in polar solvents, it is proposed that the positive ΔV̄0 reflects a favorable entropy change for the reaction toward the Z conformation. The larger entropy change of the Z form may derive from the release of water molecules from the hydration spheres of the cation and the poly[d(G‐C)] due to the formation of ionic interactions with the Z conformer. The ΔV̄0 of the transition is similar in sign and and magnitude to the calculated molar volume change of the interaction of Na+ with H2PO in water.
Inclusion of ionic interactions in force field calculations of charged biomolecules – DNA structural transitions
Authors: Klement Reinhard , Soumpasis Dikeos M. , Kitzing Eberhard V. , Jovin Thomas M.
Published: December 2004

The potential of mean force (PMF) approach for treating polyion–diffuse ionic cloud interactions [D. M. Soumpasis (1984) Proceedings of the National Academy of Sciences USA 81, 5116–5120] has been combined with the AMBER force field describing intramolecular interactions. The resultant generalized AMBER‐PMF force field enables one to treat the conformational stabilities and structural transitions of charged biomolecules in aqueous electrolytes more realistically. For example, we have used it to calculate the relative stabilities of the B and Z conformations of d(C‐G)6, and the B and heteronomous (H) conformations of dA12 · dT12, as a function of salt concentration. In the case of d(C‐G)6, the predicted B–ZI transition occurs at 2.4M and is essentially driven by the phosphate‐diffuse ionic cloud interactions alone as suggested by the results of earlier PMF calculations. The ZII conformer is less stable than the B form under all conditions. It is found that the helical parameters of the refined B and Z structures change with salt concentration. For example, the helical rise of B‐DNA increases about 10% and the twist angle decreases by the same amount above 1M NaCl.

In the range of 0.01–0.3M NaCl, the H form of dA12 · dT12 is found to be more stable than the B form and its stability increases with increasing salt concentration. The computed greater relative stability of the H conformation is likely due to noninclusion of the free energy contribution from the spine of hydration, a feature presumed to stabilize the B form of this sequence.
Electrophoretic charge density and persistence length of DNA as measured by fluorescence microscopy
Authors: Smith Steven B. , Bendich Arnold J.
Published: December 2004

Individual ethidium‐stained DNA molecules, embedded in an agarose gel made with electrophoresis buffer (0.05 molar salt), are observed using a fluorescence microscope. In the first experiment, open circular 66 kilobase pair (kbp) plasmids, immobilized by agarose fibers threaded through their centers, display entropic “rubber” elasticity. The charged molecules extend in an electric field of several volts per centimeter and contract to a compact random coil when the field is removed. The extension of the plasmids as a function of field strength is consistent with the freely jointed chain model when the effective electrophoretic charge density is set at 15 e− per persistence length. In a second experiment, stained linear 48.5 kbp DNA molecules are observed as random coils immobilized in agarose. A measure of their size, here named the “maximal‐X‐extent,” is taken for 100 molecules and found to average 1.47 μ. A Monte Carlo computer simulation of random coils (freely jointed chain model) gives the same maximal‐X‐extent value when the persistence length is set at 0.08 μ.
Microwave dielectric study on hydration of moist collagen
Authors: Shinyashiki Naoki , Asaka Nobuyuki , Mashimo Satoru , Yagihara Shin , Sasaki Naoki
Published: December 2004

Two dielectric relaxation peaks were found in moist collagen by the time domain reflectometry. The low‐frequency peak around 100 MHz moves little as the water content is varied. Its relaxation strength depends on the content and vanishes for completely dried collagen. This process is concluded to be due to water molecules strongly bound to the tropocollagen. Amount of the bound water is estimated as 0.12 g water/g collagen. Twenty‐one water molecules are bound to one repeat of the triple helix. The existence of stringlike water chains is suggested. If the water content is less than 0.5 g water/g collagen, the high frequency peak locates between those of bound and bulk water. Water among the tropocollagen is weakly bound to the collagen. In the higher region it does not change much with the content, being close to that of bulk water. The bulk water appears in this region.
Intramolecular interference effects in dynamic light scattering: Rigid double spirals and superhelical DNAs
Authors: Wu Pengguang , Song Lu , Schurr J. Michael
Published: December 2004

A theory is developed for dynamic light scattering (DLS) from rigid double spirals by treating an invisible rigid cylinder with two helical scattering stripes on opposite sides of its cylindrical surface. The exact initial, or first cumulant, diffusion coefficient Dapp(K) is obtained in terms of the translational diffusion coefficients (D∥ and D⟂) parallel and perpendicular to the symmetry axis, the rotational diffusion coefficients (D and D) around the symmetry and transverse axes, the length (L) and radius (b) of the cylindrical surface bearing the stripes, and the pitch (p). Interference effects, namely geometrical antiresonances, between strands, produce deep minima in the static structure factor S(K) and corresponding prominent peaks in Dapp(K). These peaks in Dapp(K) depend sensitively on the rotational dynamics around the symmetry axis, and nearly vanish when D = 0. Some results for single spirals are also presented. A simpler model in which scattering points are attached at opposite ends of an otherwise invisible thin rigid rod is also treated, and shown to exhibit modest minima in S(K) and corresponding maxima in Dapp(K). Confining this rod to a plane containing K enhances the amplitudes of the oscillations in S(K) and Dapp(K), as expected.

Rigid double spirals are employed as crude models for interwound supercoiled DNAs in order to assess the possible occurrence of interference effects. Although native supercoiled DNAs exhibit a cylinder diameter that is much too small to exhibit geometrical antiresonances in the presently accessible range of K2, nearly relaxed supercoiled DNAs are predicted to exhibit their first maximum in Dapp(K) just inside this range. Previously reported data for the effect of Escherichia coli single‐strand binding (ssb) protein on the DLS of supercoiled pBR322 DNA cannot be mimicked by a gradual homogeneous reduction of superhelix density with increasing ssb, but instead can be mimicked by inhomogeneous all‐or‐none binding in which uncomplexed native DNAs and nearly relaxed saturated ssb/DNA complexes coexist in varying proportions. Experimental Dapp(K) and S(K) data for a sample of relaxed pUC8 dimers display, respectively, a broad maximum and a corresponding minimum, in qualitative agreement with rough theoretical predictions.
The sieving of rod‐shaped viruses during agarose gel electrophoresis. I. Comparison with the sieving of spheres
Authors: Griess Gary A. , Moreno Elena T. , Herrmann Richard , Serwer Philip
Published: December 2004

The sieving of rod‐shaped viruses during agarose gel electrophoresis is quantitatively analyzed here with a previously proposed model [G. A. Griess et al. (1989) Biopolymers, 28, 1475–1484] that has one radius (PE) of the effective pore at each concentration of gel. By use of this model and an internal spherical size standard, a plot of electrophoretic mobility vs agarose percentage is converted to a plot of the radius of the effective sphere (effective radius) vs PE. Experimentally, when the concentration of the rod‐shaped bacteriophage, fd, is progressively increased, eventually the electrophoretic mobility of fd becomes dependent on its concentration. The concentration of fd at which this occurs decreases as the agarose concentration decreases. After avoiding this dependence on the concentration of sample, the effective radius of rod‐shaped particles, including bacteriophage fd, length variants of fd, and length variants of tobacco mosaic virus, is found to increase as PE increases until a plateau of approximately constant maximum effective radius is reached at P. In the region of this plateau, the effective sphere's measure that best approximates that of the rod is surface area. However, significant disagreement with the data exists for surface area; the maximum effective radius for fd varies as (length)0.69. For fd and its length variants, the value of 2·P/length increases from 0.21 to 0.86 as the length decreases from 2808 to 367 nm. The dependence of effective radius on PE and the proximity of 2·P to the length of the rod are explained by (a) random orientation of rods at PE values in the region of the plateau, and (b) increasingly preferential end‐first orientation (reptation) of the rod as PE decreases below P. This hypothesis of reptation is supported by a significant dependence of electrophoretic mobility on electrical potential gradient for a PE below, but not above, P. The dependence of 2·P/length on length is not rigorously understood, but is qualitatively explained by flexibility of the rods. This apparent flexibility has thus far prevented determination of a rod's axial ratio from quantitation of sieving during agarose gel electrophoresis. The electrical potential dependence of electrophoretic mobility is determined here by a procedure of two‐dimensional agarose gel electrophoresis. This procedure is also useful for detecting rod‐shaped particles in heterogeneous mixtures of predominantly spherical particles.
Stabilization of helical structure in two 17‐residue amphipathic analogues of the C‐terminal peptide of cytochrome c
Authors: Collawn James F. , Paterson Yvonne
Published: December 2004

The conformations of two 17‐residue peptide analogues derived from the C‐terminal sequence of pigeon cytochrome c (native sequence = KAERADLIAYLKQATAK) were examined in aqueous and lipid environments by CD spectroscopy. The two analogues, KKLLKKLIAYLKQATAK (K peptide), and EELLEELIAYLKQATAK (E peptide), were made amphipathic with respect to helical segregation by substituting a 6‐residue sequence at the N‐terminus of the native peptide. Their structures were compared to the native peptide under aqueous conditions of varying pH and temperature, and in the presence of liposomes composed of phosphatidylcholine and phosphatidylserine in the ratio of 9:1. The results indicated that the native peptide remains unstructured under all the conditions examined even though this region of the native molecule is surface exposed and helical. The E peptide, however, was helical under aqueous conditions at 25°C from pH 2–10 with a maximum helicity at pH 4 (54% helix from analysis of CD data). The ellipticity of the E peptide at pH 4 and 8 was concentration dependent, indicating an aggregation phenomenon. In studies in which the CD spectrum was measured at different temperatures, the E peptide became more helical at lower temperatures at pH 4 but not at pH 8. Upon interaction with a lipid membrane in the form of liposomes, there appeared to be a slight destabilization in the structure of the E peptide. The K peptide in an aqueous environment behaved like the native peptide in that it was structureless at all pHs and temperatures examined. In the presence of liposomes, however, this peptide had a high helical content (75% helix from analysis of CD data). These findings suggest that while stabilization of the helix dipole with negative charges at the N‐terminus are important in inducing helical conformation in the E peptide, hydrophobic interactions created during aggregation appear to provide the principal stabilizing force. The results with the K peptide demonstrate that the positive N‐terminal sequence of this peptide is able to interact with the negatively charged head groups in the phospholipid membrane in such a fashion as to stabilize a helical structure that is not apparent in an aqueous environment alone.
Viscoelastic properties of solutions of ovine submaxillary mucin
Authors: Soby Lynn M. , Jamieson Alexander M. , Blackwell John , Jentoft Neil
Published: December 2004

The linear viscoelastic and rheological properties of high molecular weight ovine submaxillary mucin (OSM) solution have been investigated in terms of the Newtonian steadyflow viscosity \documentclass{article}\pagestyle{empty}\begin{document}$ [\eta (\dot{\gamma})] $\end{document}, the complex oscillatory viscosity [η*(ω)], and the storage and loss shear moduli [G′(ω) and G″(ω)]. It was observed that \documentclass{article}\pagestyle{empty}\begin{document}$ \eta (\dot{\gamma}) $\end{document}, η*(ω), and G′(ω) are always higher when OSM is dissolved in 0.1M NaCl than when at the same concentration in 6M GdnHCl. This is consistent with previous observations that submaxillary mucins self‐associate in 0.1M NaCl to form large aggregates, which are disrupted in 6M GdnHCl. As the OSM concentration increases, the appearance of a plateau shear modulus indicates the formation of a gel network in both solvents. The results suggest gelation involves specific intermolecular interactions, perhaps due to hydrophobic forces between interdigitated oligosaccharide side chains. The viscoelastic behavior of OSM solution at high concentration is thus similar to that reported in the literature for porcine gastric mucin (PGM). However, the OSM gels are mechanically weaker, having moduli that are an order of magnitude lower thatn those for PGM gels of comparable concentration. The oligosaccharide side chains of OSM consist of only 1–2 sugar units compared to 10–15 for PGM, but it appears that this is sufficient to allow for intermolecular interaction and the formation of weak gels.
Alanyl dipeptide potential‐derived net atomic charges and bond dipoles, and their variation with molecular conformation
Authors: Williams Donald E.
Published: December 2004

The elctric potential around the alanyl dipeptide in various conformations was calculated from ab initio 6–31G wave functions. Seven conformations were selected to correspond to calculated local energy minima of the isolated molecule. Five additional conformations were selected corresponding to the alanylalanine crystal structure and the polypeptide conformations in a right‐handed α‐helix, left‐handed α‐helix, parallel β‐sheet, and anti‐parallel β‐sheet. The electric potential surrounding each conformer was fitted with either net charges at atomic sites or dipolles at bond sites by least squares. Either choice reproduced the electric potential with relative rms deviations of 1.9–4.8%. Values for net atomic charges or bond dipoles were usually in line with expectations based on electronegativity. The imino and carbonyl groups showed their expected polarities, although there were considerable deviations from zero group charge. Net atomic charges on and near the α‐carbon changed substantially with the conformation angles; bond dipoles around the α‐carbon showed analogous behavior.
Conformational studies of cyclic peptide structures in solution from 1H‐Nmr data by distance geometry calculation and restrained energy minimization
Authors: Senn Hans , Loosli Hans‐Rudolf , Sanner Michel , Braun Werner
Published: December 2004

The three‐dimensional structure of a cyclic bouvardin analogue, cyclo (‐Pro‐MeTyr‐Ala‐MeTyr‐MeTyr‐D‐Ala‐) has been determined by distance geomtry calculation and restrained energy minimization from nmr data. The preparation of the input for the distance geometry calculations, the modification of the amino acid library, and the analysis of the structures were done with the aid of a recently developed software package, GEOM. A great variety of different initial structures were explored to check the uniqueness of the determined solution structure. Calculations with 500 different initial structures and two different strategies led to a uniquely determined backbone conformation with a root mean square deviations value of 0.4 Å. The backbone structure consists of two β‐turns, a β‐II turn at Pro1‐MeTyr2, and a β‐VI turn at MeTyr4‐MeTyr5. The efficiency of the two calculation strategies were compared in order to propose an optimal means for performing distance geometry calculations with cyclic structures.
Self‐assembly of a bioelastomeric structure: Solution dynamics and the spinodal and coacervation lines
Authors: Sciortino F. , Urry D. W. , Palma M. U. , Prasad K. U.
Published: December 2004

The stability, metastability, and instability regions of aqueous solutions of a representative synthetic bioelastomeric polymer, poly (Val‐Pro‐Gly‐Val‐Gly), were determined by a combined used of elastic and quasi‐elastic light scattering experiments. The approach followed here offers the attractive advantage of singling out the relevant contributions to the total scattering even in the presence of traces of noninteracting larger sized impurities. Conclusions so reached were checked by means of independent experiments. The present results provide descriptions of the very early events in the physics of bioelastogenesis in terms of general polymer science and phase transitions, and in terms of an unexpected possible functional role of density fluctuations.
A 1.8 Å resolution potential function for protein folding
Authors: Crippen Gordon M. , Snow Mark E.
Published: December 2004

A general method is presented for constructing a potential function for approximate conformational calculations on globular proteins. The method involves solving a nonlinear program that seeks to adjust the potential's parameters in such a way that a minimum near the native remains a minimum and does not move far away, while any alternative minima shift so as to remain local minima but eventually rise higher than the level of the near‐native minimum. Although the potential trades computational speed for detail by representing each amino acid residue as only a single point, correct secondary structural preferences and reasonable tertiary folding can be built into the potential in an entirely routine way. The potential has been parameterized to agree with the crystal structure of avian pancreatic polypeptide (having 36 residues) in the sense that the lowest minimum found (‐407 arbitrary units) is reasonably close to the native (1.8 Å rms interresidue distance deviation). In contrast, the lowest nonnative conformation found after extensive searches by a variety of methods was −399 units and 7.5 Å away. Such potentials may prove to be useful in predicting approximate tertiary structure from amino acid sequence, if they can be generalized to apply to more than one protein.
Theoretical studies on the conformation of saccharides. XIV. Structure and conformational properties of the glycosylamines
Authors: Kožár Tibor , Tvaroška Igor
Published: December 2004

The 2‐methylaminotetrahydropyran was used as a model to study conformational properties of the N‐glycosidic linkage in glycosylamines. Relaxed two‐dimensional conformational (Φ,Ψ) maps in 20 solvents were calculated by a method in which the total energy is divided into the energy of the isolated molecule and the solvation energy. Molecular geometry optimization has been carried out for each conformer using the quantum chemical method PCILO. The calculated variations of the geometry are consistent with the results obtained by the statistical analysis of available experimental data retrieved from the Cambridge Structural Database. The calculated abundances of conformers show that the polarity of the solvent has little effect on the anomeric ratio, and the form having the methylamino group equatorial is favored in all considered solvents.
Binding of cationic dyes to potassium alginate: A spectrophotometric and dichroic probe
Authors: Pal Medini Kanta , Mandal Nemai
Published: December 2004

Acridine orange (AO) binds to potassium alginate (KAlg) stoichiometrically as is evidenced from conductometric and spectrofluorometric titrations. However, AO as well as methylene blue (MB) exhibits weak metachromasia and no induced dichroism at any sensible polymer to dye ratio (P / D). KAlg induces large blue shifts (by as much as 125 nm) of the λmax of the strongly aggregating dyes 1, 9‐dimethylmethyleneblue (DMMB) and pinacyanol at reasonable P / D values; KAlg also induces strong dichroism in these dyes. The signs of the induced CD spectra indicate KAlg to have a left‐handed helical conformation. This polymer also induces red‐shifted J band and dichroism in the dye N‐N′‐diethylpseudoisocyanine (PIC) at high P / D under which condition the signs of CD spectra in DMMB reverse with drastic reduction in [θ] values. This reversal of sign of CD or induction of J band in PIC at only high KAlg concentrations does not involve any conformational change in the polymer as indicated by the insensitivity of the UV‐CD spectrum of KAlg as a function of concentration.
On the dependence of molecular conformation on the type of solvent environment: A molecular dynamics study of cyclosporin A
Authors: Lautz J. , Kessler H. , van Gunsteren W. F. , Weber H.‐P. , Wenger R. M.
Published: December 2004

The dependence of the conformation of cyclosporin A (CPA), a cyclic undecapeptide with potent immunosuppressive activity, on the type of solvent environment is examined using the computer simulation method of molecular dynamics (MD). Conformational and dynamic properties of CPA in aqueous solution are obtained from MD simulations of a CPA molecule dissolved in a box with water molecules. Corresponding properties of CPA in apolar solution are obtained from MD simulation of CPA in a box with carbontetrachloride. The Results of these simulations in H2O and in CCl4 are compared to each other and to those of previous simulations of crystalline CPA and of an isolated CPA molecule.

The conformation of the backbone of the cyclic polypeptide is basically independent of the type of solvent. In aqueous solution the β‐pleated sheet is slightly weaker and the γ‐turn is a bit less pronounced than in apolar solution. Side chains may adopt different conformations in different solvents. In apolar solution the hydrophobic side chain of the MeBmt residue is in an extended conformation with its hydroxyl group hydrogen bonded to the backbone carbonyl group. In aqueous solution this hydrophobic side chain folds over the core of the molecule and the mentioned hydrogen bond is broken in favor of hydrogen bonding to water molecules. The conformation obtained from the MD simulation in CCl4 nicely agrees with experimental atom‐atom distance data as obtained from nmr experiments in chloroform. In aqueous solution the relaxation of atomic motion tends to be slower than in apolar solution.
Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues
Authors: Luan Chi‐Hao , Harris R. Dean , Prasad Kari U. , Urry Dan W.
Published: December 2004

Differential scanning calorimetry studies have been carried out on the sequential polypeptide of elastin, (L‐Val1–L‐Pro2–Gly3–L‐Val4–Gly5)n, abrreviated as PPP, and its more hydrophobic analogues (L‐Val1–L‐Pro2–Gly3–L‐Val4–Gly5)n, referred to as Leu1‐PPP, and (L‐Ile1–L‐Pro2–Gly3–L‐Val4–Gly5)n, referred to as Ile1‐PPP. Consistent with inverse temperature transitions, the temperatures of the transitions for which maximum heat absorption occurs are inversely proportional to the hydrophobicities of the polypentapeptides (31°C for PPP, 16°C for Leu1‐PPP, and 12°C for Ile1‐PPP), and the endothermic heats of the transitions are small and increase with increasing hydrophobicity, i.e., 1.2, 2.9, and 3.0 kcal/mol pentamer for PPP, Leu1‐PPP, and Ile1‐PPP, respectively. Previous physical characterizations of the polypentapeptides have demonstrated the occurrence of an inverse temperature transition since increase in order, as the temperature is raised above that of the transition, has been repeatedly observed using different physical characterizations. Furthermore, the studies demonstrated indentical conformations for PPP and Ile1‐PPP above and below the transition. Both heats and temperature of the transitions vary with hydrophobicity, but not in simple proportionality.
Viscoelastic properties of alginate aqueous solutions in the presence of salts
Authors: Matsumoto Takayoshi , Mashiko Kimio
Published: December 2004

The influence of added salts on the dynamic viscoelastic properties are investigated for aqueous solutions of alginates that have various molecular weights and mannuronate/guluronate (M/G) ratios. The dynamic moduli of the systems increase with increasing concentration of the added salt in the low‐frequency region. The effect is notable in the order of KCl < NaCl < MgCl2 ≪ CaCl2. The values of the dynamic moduli in the rubbery plateau are independent of the addition of the salts, irrespective of the M/G ratio of the alginate. These facts strongly suggest that the structure that is formed by the interaction between the alginates and the metal ions does not work as cross‐linking points but as heterogeneous relaxation units having a relatively long relaxation time from a rheological viewpoint.
Analysis of melting transitions of the DNA hairpins formed from the oligomer sequences d[GGATAC(X)4GTATCC] (X = A, T, G, C)
Authors: Paner Teodoro M. , Amaratunga Mohan , Doktycz Mitchel J. , Benight Albert S.
Published: December 2004

Optical melting transitions of the short DNA hairpins formed from the self‐complementary DNA oligomers d[GGATACX4GTATCC] where X = A, T, G, or C measured in 100 mM NaCl are presented. A significant dependence of the melting transitions on loop sequence is observed and transition temperatures, tm, of the hairpins vary from 58.3°C for the T4 loop hairpin to 55.3°C for the A4 loop. A nearest‐neighbor sequence‐dependent theoretical algorithm for calculating melting curves of DNA hairpins is presented and employed to analyze the experimental melting transitions. Experimental melting curves were fit by adjustment of a single theoretical parameter, Fend(n), the weighting function for a hairpin loop comprised of n single‐strand bases. Empirically determined values of Fend(n) provide an evaluation of the free‐energy of hairpin loop formation and stability. Effects of heterogeneous nearest‐neighbor sequence interactions in the duplex stem on hairpin loop for mation were investigated by evaluating Fend(n) in individual fitting procedures using two of the published sets of nearest‐neighbor stacking interactions in DNA evaluated in 100 mM NaCl and given by Wartell and Benight, 1985. In all cases, evaluated values of Fend(n) were obtained that provided exact theoretical predictions of the experimental transitions.

Results of the evaluations indicate: (1) Evaluated free‐energies of hairpin loop formation are only slightly dependent on loop sequences examined. At the transition temperature, Tm, the free‐energy of forming a loop of four bases is approximately equal for T4, G4, or C4 loops and varies from 3.9 to 4.8 kcal/mole depending on the set of nearest‐neighbor interactions employed in the evaluations. This result suggests, in light of the observed differences in stability between the T4, G4, and C4 loop hairpins, that sequence‐dependent interactions between base residues of the loop are most likely not the source of the enhanced stability of a T4 loop. In contrast, the evaluated free‐energy of forming an A4 loop is approximately 400 cal/mole higher for each nearest‐neighbor set indicating unfavorable interactions between A bases in a loop‐affect loop formation and overall hairpin stability, (2) The absolute value for the free‐energy of loop formation at the Tm of each hairpin varies by about 1 kcal/mole depending on the set of nearest‐neighbor interactions employed and the relative hierarchy of stability for each loop is conserved for different nearest neighbor sets, (3) The melting process of each hairpin deviates from strict two‐state behavior in the order according to loop sequence of T > A > G > C, (4) Results of our analysis are compared with the early work of Scheffler et al., 1970 on the hairpins formed from the copolymer sequences d(T – A)q where q = 9–21. Comparisons with the more recent works a DNA dumbbell (Benight et al., 1988) and the very similar DNA hairpins studied by Senior et al., 1988 are presented.
Normal mode theory for the Brownian dynamics of a weakly bending rod: Comparison with Brownian dynamics simulations
Authors: Song Lu , Allison Stuart A. , Schurr J. Michael
Published: December 2004

A normal mode theory is developed for the Brownian dynamics of weakly bending rods with preset hydrodynamic interactions. The rod is replaced by a chain of contiguous spheres whose radius is chosen to yield the appropriate uniform translational and rotational diffusion coefficients. Despite the inclusion of preset hydrodynamic interactions in the dynamical operator, its normal modes are not coupled by the potential energy, so their amplitudes remain pairwise “orthogonal” under equilibrium averaging. The uniform translational and rotational diffusion coefficients obtained from Langevin theory are shown to be identical to those obtained from the Kirkwood algorithm, despite their rather different appearance. An expression is given for the mean squared angular displacement 〈Δxm(t)2〉 of the mth bond vector around the instantaneous x axis (perpendicular to the end‐to‐end vector z). Necessary algorithms are presented for the numerical evaluation of all quantities. The normal mode theory is compared with Brownian dynamics simulations for the same model by examining 3〈Δxm(t)2〉 for the central bond vector of rods comprising 10 and 30 subunits with various persistence lengths. The normal mode theory works very well for all times for L/P ≲ 0.6, where P = κ/kBT is the persistence length and κ is the bending rigidity. With increasing flexibility, the domain of validity of the normal mode theory is restricted to shorter times, where violations of the weak bending approximation are less severe. However, increasing the length of the rod from 10 to 30 subunits yields improved agreement with the simulations for the same and even longer times. This latter effect is tentatively attributed to the greater fluctuating tension in the longer chains, which acts to retard the rotational relaxation in the simulations, but is not taken into account in the present normal mode theory.
Application of the distance geometry algorithm to cyclic oligopeptide conformation searches
Authors: Peishoff Catherine E. , Dixon J. Scott , Kopple Kenneth D.
Published: December 2004

The distance geometry algorithm as embodied in the program DGEOM was examined as a method for searching cyclic peptide conformations. Conformations were randomly generated using covalent distance and chirality constraints, but torsion angle rather than distance sampling was used for 1, 4 relationships. Structures so generated were energy minimized by a fixed number of iterations using the molecular mechanics program AMBER 3.0; electrostatic terms were excluded in the minimization. The effectiveness of this procedure in sampling conformational space for cyclic peptides was measured by the ability to recover, from a set of 500 structures, conformations similar to those experimentally observed for six cyclic peptides containing from 8 to 20 rotatable backbone bonds. Structures similar to experimental structures were recovered in a 16‐bond case, but not for a 20‐bond example. The method was also applied, with constraints on the peptide bond angles ω, to an additional example containing 21 ring bonds.
Crystal structure and solution conformation of S,S′‐bis(Boc‐Cys‐Ala‐OMe): Intramolecular antiparallel β‐sheet conformation of an acyclic cystine peptide
Authors: Raj P. Antony , Soni S. D. , Ramasubbu N. , Bhandary K. K. , Levine M. J.
Published: December 2004

The conformation of the acyclic biscystine peptide S,S′‐bis(Boc‐Cys‐Ala‐OMe) has been studied in the solid state by x‐ray diffraction, and in solution by1H‐ and13C‐nmr, ir, and CD methods. The peptide molecule has a twofold rotation symmetry and adopts an intramolecular antiparallel β‐sheet structure in the solid state. The two antiparallel extended strands are stabilized by two hydrogen bonds between the Boc CO and Ala NH groups [N ⃛O 2.964 (3) Å, O ⃛HN 2.11 (3) Å, and NH ⃛O angle 162 (3)°]. The disulfide bridge has a right‐handed conformation with the torsion angle CβSSCβ = 95.8 (2)°. In solution the presence of a twofold rotation symmetry in the molecule is evident from the1H‐ and13C‐nmr spectra. 1H‐nmr studies, using solvent and temperature dependencies of NH chemical shifts, paramagnetic radical induced line broadening, and rate of deuterium‐hydrogen exchange effects on NH resonances, suggest that Ala NH is solvent shielded and intramolecularly hydrogen bonded in CDCl3 and in (CD3)2SO. Nuclear Overhauser effects observed between Cys CαH and Ala NH protons and ir studies provide evidence of the occurrence of antiparallel β‐sheet structure in these solvents. The CD spectra of the peptide in organic solvents are characteristic of those observed for cystine peptides that have been shown to adopt antiparallel β‐sheet structures.
A polarized and depolarized dynamic light scattering study of the tRNAphe conformation in solution
Authors: Patkowski A. , Eimer W. , Dorfmüller Th.
Published: December 2004

The dynamics of tRNAphe from brewer's yeast in solution was studied over a broad concentration and temperature range by polarized and depolarized dynamic light scattering. It is shown that measurements of the depolarized Rayleigh spectrum with a high‐resolution confocal Fabry‐Perot interferometer provide very accurate values for the rotational diffusion coefficient of the biopolymer. The translational diffusion coefficient was determined by polarized photon correlation spectroscopy. A combination of both transport coefficients allows one to calculate the hydrodynamic size of tRNAphe using the Perrin equations for an biaxial ellipsoid. Within a temperature range from 9 to 45°C, the tRNAphe molecule adopts a nearly spherical shape. The dimensions are similar to the previously proposed U‐shaped structure. In the melting region a second relaxation process was observed that is attributed to the collective reorientation of the bases. The concentration dependence of the rotational diffusion coefficient of tRNAphe in the concentration range of 2–75 mg/mL exhibits a slightly positive slope, in agreement with previous experimental findings and in contradiction to the theoretical predictions based on hydrodynamic interactions in solution.
Computer modeling studies of ribonuclease T1–guanosine monophosphate complexes
Authors: Balaji P. V. , Rao V. S. R. , Saenger W.
Published: December 2004

The three‐dimensional structures of ribonuclease (RNase) T1 complexes with the inhibitors 2′‐guanylic acid (2′‐GMP), 3′‐guanylic acid (3′‐GMP), and 5′‐guanylic acid (5′‐GMP) were predicted by energy minimization studies. It is shown that these inhibitors can bind to RNase T1 in either of the ribose puckered conformations (C2′‐endo and C3′‐endo) in solid state and exist in significant amounts in both forms in solution. These studies are in agreement with the x‐ray crystallographic studies of the 2′‐GMP–Lys25–RNase T1 complex, where the inhibitor binds in C2′‐endo puckered conformation. These results are also in good agreement with the available 1H‐nmr results of Inagaki et al. [(1985) Biochemistry 24, 1013–1020], but differ from their conclusions where the authors favor only the C3′‐endo ribose conformation for all the three inhibitors. The calculations explain the apparent discrepancies in the conclusions drawn by x‐ray crystallographic and spectroscopic studies. An extensive hydrogen‐bonding scheme was predicted in all the three complexes. The hydrogen‐bonding scheme predicted for the 2′‐GMP (C2′‐endo)–RNase T1 complex agrees well with those reported from x‐ray crystallographic studies. In all three complexes the base and the phosphate bind in nearly identical sites independent of the position of the phosphate or the ribose pucker. The glycosyl torsion angle favors a value in the +syn range in the 2′‐GMP(C2′‐endo)–RNase T1, 3′‐GMP(C2′‐endo)–RNase T1, and 3′‐GMP(C3′‐endo)–RNase T1 complexes; in the high‐synrange in the 2′‐GMP(C3′‐endo)–RNase T1 complex; and in the ‐syn range in the 5′‐GMP(C2′‐endo)–RNase T1, and 5′‐GMP(C3′‐endo)–RNase T1 complexes. These results are in agreement with experimental studies showing that the inhibitory power decreases in the order 2′‐GMP > 3′‐GMP > 5′‐GMP, and they also explain the high pKa value observed for Glu58 in the 2′‐GMP–RNase T1 complex.
Conformational studies on peptides with proline in the right‐handed α‐helical region
Authors: Sankararamakrishnan R. , Vishveshwara Saraswathi
Published: December 2004

The proline residues in proteins are known to play an important structural role. Recently, the role of a proline residue in the middle of right‐handed α‐helical segments of peptides has been the focus of attention. This role seems to be particularly important in the case of membrane proteins and in the tight packing of globular proteins. In the present study the right‐handed α‐helical region of the Ala‐Pro dipeptide and of polypeptides containing this group have been investigated. Crystal structures of proline‐containing α‐helices from some proteins have been analyzed and energy minimization studies on some model fragments containing Ala‐Pro in the right‐handed α‐helical conformation have been carried out using flexible geometry. The present calculations indicate that the right‐handed α‐helical region of conformational space is an energetically favored region that can also accommodate Ala‐Pro in longer segments of right‐handed α‐helix. This is achieved due to minor variations in some of the internal parameters. Deviations in the backbone parameters of proline in the right‐handed α‐helix lead to a kink of about 23° in the helix axis. These deviations have been characterized and a set of standard values has been suggested for producing such a kink. These values can be used for model building and as starting points for further minimization studies. Previous energy minimization studies have been done using rigid geometry. This may explain why the minimum for Ala‐Pro in the right‐handed α‐helical region has not been recognized thus far.
A hierarchical “nesting” approach to describe the stability of alpha helices with side‐chain interactions
Authors: Robert Charles H.
Published: December 2004

A straightforward hierarchical statistical–mechanical approach is shown to enable one to describe the stability of the alpha helix in the presence of side‐chain interactions. The formulation can be used with even the simple nearest‐neighbor models and it is demonstrated explicitly with the popular 2 × 2 Zimm‐Bragg model [B. H. Zimm and J. K. Bragg (1959) J. Chem. Physics 31, 526–535]. It involves a conceptual dissection of the polypeptide chain into interacting blocks; the behavior of any block with side‐chain interactions is treated then with conventional binding polynomial techniques. This dissection is a manifestation of “nesting,” which is a hierarchical framework for the description of the behavior of complex macromoecules [C. H. Robert, H. Decker, B. Richey, S. J. Gill, and J. Wyman (1987) Proc. Natl. Acad. Sci. 84, 1891–1895]. The method is demonstrated through applications to existing detailed data for the pH and salt dependences of the helix–coil transition in the S peptide and in synthetic peptides.