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Results for “Molecular Dynamic simulation”

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At least 217 records · Page 12Linked to original sources

PubMed2002

Molecular dynamics simulation of polymer helix formation using rigid-link methods.

Molecular dynamics simulations are used to study structure formation in simple model polymer chains that are subject to excluded volume and torsional interactions. The changing conformations exhibited by chains of different lengths under gradual cooling are followed until each reaches a state from which no further change is possible. The interactions are chosen so that the true ground state is a helix, and a high proportion of simulation runs succeed in reaching this state; the fraction that manages to form defect-free helices is a function of both chain length and cooling rate. In order to demonstrate behavior analogous to the formation of protein tertiary structure, additional attractive interactions are introduced into the model, leading to the appearance of aligned, antiparallel helix pairs. The simulations employ a computational approach that deals directly with the internal coordinates in a recursive manner; this representation is able to maintain constant bond lengths and angles without the necessity of treating them as an algebraic constraint problem supplementary to the equations of motion.

Journal Article↗

PubMed2002

Molecular dynamics simulations of crystallization of hard spheres.

We have carried out molecular dynamics simulations of the crystallization of hard spheres modeling colloidal systems that are studied in conventional and space-based experiments. We use microscopic probes to investigate the effects of gravitational forces, polydispersity, and of bounding walls on the phase structure. The simulations employed an extensive exclusive particle grid method and the type and degree of crystalline order was studied in two independent ways: by the structure factor, as in experiments, and through local rotational invariants. We present quantitative comparisons of the nucleation rates of monodisperse and polydisperse hard-sphere systems and benchmark them against experimental results. We show how the presence of bounding walls leads to wall-induced nucleation and rapid crystallization, and discuss the role of gravity on the dynamics of crystallization.

Journal Article↗

PubMed2000

Orientation dependence in molecular dynamics simulations of shocked single crystals

We use multimillion-atom molecular dynamics simulations to study shock wave propagation in fcc crystals. As shown recently, shock waves along the <100> direction form intersecting stacking faults by slippage along 111 close-packed planes at sufficiently high shock strengths. We find even more interesting behavior of shocks propagating in other low-index directions: for the <111> case, an elastic precursor separates the shock front from the slipped (plastic) region. Shock waves along the <110> direction generate a leading solitary wave train, followed (at sufficiently high shock speeds) by an elastic precursor, and then a region of complex plastic deformation.

Journal Article↗

PubMed2001

Comment on "Efficient stress relaxation in molecular dynamics simulations of semiflexible n-alkanes".

Contrary to the findings of Mülders, Toxvaerd, and Kneller [Phys. Rev. E 58, 6766 (1998)] (MTK), we are unable to discern any difference in the behavior of long chain alkanes simulated by molecular dynamics at constant pressure using either atomic or molecular scaling schemes. This result confirms our previous study [M. Marchi and P. Procacci, J. Chem. Phys. 109, 5194 (1998)] on hydrated proteins published at the same time as the MTK's paper. This Comment indicates that errors in the calculation of the pressure tensor might be responsible for at least a part of the MTKs results.

Letter↗

PubMed1996

The consistency of large concerted motions in proteins in molecular dynamics simulations.

A detailed investigation is presented into the effect of limited sampling time and small changes in the force field on molecular dynamics simulations of a protein. Thirteen independent simulations of the B1 IgG-binding domain of streptococcal protein G were performed, with small changes in the simulation parameters in each simulation. Parameters studied included temperature, bond constraints, cut-off radius for electrostatic interactions, and initial placement of hydrogen atoms. The essential dynamics technique was used to reveal dynamic differences between the simulations. Similar essential dynamics properties were found for all simulations, indicating that the large concerted motions found in the simulations are not particularly sensitive to small changes in the force field. A thorough investigation into the stability of the essential dynamics properties as derived from a molecular dynamics simulation of a few hundred picoseconds is provided. Although the definition of the essential modes of motion has not fully converged in these short simulations, the subspace in which these modes are confined is found to be reproducible.

Antigens, Bacterial↗

PubMed1988

Molecular dynamics simulations of ribonuclease T1. Effect of solvent on the interaction with 2'GMP.

Molecular dynamics simulations in vacuum and with a water sphere around the active site were performed on the 2'GMP-RNase T1 complex. The presence of water led to the maintenance of the 2'-GMP-RNase T1 interactions as compared to the X-ray structure, including the hydrogen bonds implicated in the enzyme-inhibitor recognition process. The sidechain of His92 in the molecular dynamics water simulation, however, hydrogen bonds directly to the phosphate of 2'GMP in contrast to the X-ray structure but in support of the role of that residue in the enzyme's catalytic mechanism. Fluctuations of active-site residues are not strongly influenced by water, possibly owing to the exclusion of water by the bound 2'GMP, which did show an increase in mobility. Analysis of the 2'GMP-RNase T1 interactions versus time reveal an equilibrium fluctuation in the presence of water, leading to a less favorable 2'GMP-RNase T1 interaction energy, suggesting a possible relationship between picosecond fluctuations and inhibitor dissociation occurring in the millisecond time domain.

Endoribonucleases↗

PubMed2001

Folding-unfolding of goat alpha-lactalbumin studied by stopped-flow circular dichroism and molecular dynamics simulations.

Folding reaction of goat alpha-lactalbumin has been studied by stopped-flow circular dichroism and molecular dynamics simulations. The effects of four single mutations and a double mutation on the stability of the protein under a native condition were studied. The mutations were introduced into residues located at a hydrophobic core in the alpha-domain of the molecule. Here we show that an amino acid substitution (T29I) increases the native-state stability of goat alpha-lactalbumin against the guanidine hydrochloride-induced unfolding by 3.5 kcal/mol. Kinetic refolding and unfolding of wild-type and mutant goat alpha-lactalbumin measured by stopped-flow circular dichroism showed that the local structure around the Thr29 side chain was not constructed in the transition state of the folding reaction. To characterize the local structural change around the Thr29 side chain to an atomic level of resolution, we performed high-temperature (at 400 K and 600 K) molecular dynamics simulations and studied the structural change at an initial stage of unfolding observed in the simulation trajectories. The Thr29 portion of the molecule experienced structural disruption accompanied with the loss of inter-residue contacts and with the water molecule penetration in the 400-K simulation as well as in four of the six 600-K simulations. Disruption of the N-terminal portion was also observed and was consistent with the results of kinetic refolding/unfolding experiments shown in our previous report.

Animals↗

PubMed1996

Molecular dynamics simulations of isolated transmembrane helices of potassium channels.

In the middle of the S6 helix in voltage-gated potassium channels there is a highly conserved Pro-Val-Pro motif, while the equivalent M2 helix of inward rectifier potassium channels contains a conserved glycine residue in a comparable position. The structural implications of these conserved motifs are of interest given the evidence that S6 and M2 are components of the lining of their respective pores. Multiple sequence alignment and TM helix prediction methods were used to define consensus regions for S6 and M2. Ensembles of 50 structures for each helix were generated by simulated annealing and restrained molecular dynamics. Time-dependent fluctuations of S6 and M2 were investigated by long time scale molecular dynamics simulations on representative members of each ensemble carried out in vacuo in the presence and absence of a hydrophobic potential that mimics a lipid bilayer. The results are discussed in terms of the structural basis of the kink in S6 and M2 and of a putative functional role for flexible helices as "molecular swivels."

Amino Acid Sequence↗

PubMed2002

Flexibility in monomeric Cu,Zn superoxide dismutase detected by limited proteolysis and molecular dynamics simulation.

Limited proteolysis by trypsin of monomeric Cu,Zn superoxide dismutase from Escherichia coli induces a specific cleavage of the polypeptide chain at the level of Lys60 located in the S-S subloop of loop 6,5 where, when compared to the eukaryotic enzyme, a seven-residues insertion, completely exposed to the solvent, is observed. This result suggests that this subloop is disordered and flexible, thus enabling binding and adaptation to the active site of the proteolytic enzyme. Indeed, molecular dynamics simulation indicates that the S-S subloop undergoes high fluctuations and that its high flexibility coupled to an high solvent accessibility can explain the specific bond selection of the protease. As a matter of fact, of the possible 14 solvent accessible proteolytic sites only the Lys60 flexible site is cleaved. High flexibility and solvent exposure are confirmed by the short water residence time for the residues corresponding to the cleavage site evaluated by molecular dynamics simulation. These experiments demonstrate that molecular dynamics simulation and limited proteolysis are complementary and unambiguous tools to identify flexible sites in proteins.

Amino Acid Sequence↗

PubMed1999

Towards molecular dynamics simulation of large proteins with a hydration shell at constant pressure.

Molecular dynamics simulation of a large protein in explicit water with periodic boundary conditions is extremely demanding in terms of computation time. Consequently, we have sought approximations of the solvent environment that model its important features. Here, we describe our SAPHYR (Shell Approximation for Protein HYdRation) model in which the protein is surrounded by a shell of water molecules maintained at constant pressure. In addition to the usual pairwise interatomic interactions, these water molecules are subjected to forces approximating van der Waals and dipole-dipole interactions with the implicit surrounding bulk solvent. The SAPHYR model is tested for a system of one argon atom in water and for the protein ubiquitin, and then applied to cytochrome P450cam, a protein with over 400 residues. The results demonstrate that structural and dynamic properties of the simulated systems are improved by use of the SAPHYR model, and that this model provides a significant computational saving over simulations with periodic boundary conditions.

Algorithms↗

PubMed2002

Density functional theory for efficient ab initio molecular dynamics simulations in solution.

We present a density functional for first-principles molecular dynamics simulations that includes the electrostatic effects of a continuous dielectric medium. It allows for numerical simulations of molecules in solution in a model polar solvent. We propose a smooth dielectric model function to model solvation into water and demonstrate its good numerical properties for total energy calculations and constant energy molecular dynamics.

Algorithms↗

PubMed2000

Molecular dynamics simulation and nuclear magnetic resonance studies of the terminal glucotriose unit found in the oligosaccharide of glycoprotein precursors.

The trisaccharide alpha-d-Glcp-(1 --> 2)-alpha-d-Glcp-(1 --> 3)-alpha-d-Glcp-OMe, a model for the terminal glucotriose in Glc(3)Man(9)GlcNAc(2) in glycoprotein precursors, has been investigated by computer simulations and NMR spectroscopy. Molecular dynamics simulations were performed for 1 ns in aqueous solution and 20 ns in vacuo using the CHARMM-based force fields PARM22 and CHEAT95. An additional Monte Carlo simulation with the HSEA force field was also carried out. Experimental NMR data in water solution was obtained from measurement of long-range (1)H,(13)C heteronuclear trans-glycosidic coupling constants, (3)J(H,C), using one-dimensional Hadamard spectroscopy. Calculation of the (3)J(H,C) values from the simulations showed a varying degree of agreement to experimental data. It could be shown from simulation that the φ torsion angles differed, which was corroborated by the NMR measurements. Analyses were done of radial distribution functions and of hydrogen bonds. It was suggested that intermolecular hydrogen bonds were present, but in contrast to simulation the results from NMR spectroscopy did not support any major contribution. Hence, their influence on the conformation of the trisaccharide is rather small. Comparison of (1)H NMR chemical shifts for the trisaccharide and the glucotriose in Glc(3)Man(8)GlcNAc revealed high similarity. However, the derived conformation of the model substance in this work differed at one glycosidic torsion angle compared to the glucotriose on a large oligosaccharide.

Carbohydrate Conformation↗

PubMed2003

Molecular dynamics simulations on SDF-1alpha: binding with CXCR4 receptor.

Insights into the interacting mode of CXCR4 with SDF-1alpha are crucial in understanding the structural and functional characteristics of CXCR4 receptor. In this paper a computational pipeline, integrating protein structure prediction, molecular dynamics simulations, automated molecular docking, and Brownian dynamics simulations were employed to investigate the dynamic and energetic aspects of CXCR4 associating with SDF-1alpha. The entire simulation revealed the surface distribution feature of electrostatic potentials and conformational "open-close" process of the receptor. The possible binding conformation of CXCR4 was identified, and the CXCR4-SDF-1alpha binding complex was generated. Arg188-Glu277 salt bridge plays an important role for both the extracellular domain conformational change and SDF-1alpha binding. Two binding sites were mapped at the extracellular domain (Site 1) and inside the transmembrane domain (Site 2), which are composed of conserved residues. Sites 1 and 2 contribute approximately 60% and 40% to the binding affinity with SDF-1alpha, respectively. The binding model is in agreement with most of the experimental data. Transmembrane VI has more significant motion in the harmonious conformational transition of CXCR4 during SDF-1alpha binding, which may be possibly associated with signal transduction. Based on the modeling and simulation, a binding mechanism hypothesis between CXCR4 and SDF-1alpha and its relationship to the signal transduction has been proposed.

Algorithms↗

PubMed1998

Hydrogen bonding in helical polypeptides from molecular dynamics simulations and amide hydrogen exchange analysis: alamethicin and melittin in methanol.

Molecular dynamics simulations of ion channel peptides alamethicin and melittin, solvated in methanol at 27 degrees C, were run with either regular alpha-helical starting structures (alamethicin, 1 ns; melittin 500 ps either with or without chloride counterions), or with the x-ray crystal coordinates of alamethicin as a starting structure (1 ns). The hydrogen bond patterns and stabilities were characterized by analysis of the dynamics trajectories with specified hydrogen bond angle and distance criteria, and were compared with hydrogen bond patterns and stabilities previously determined from high-resolution NMR structural analysis and amide hydrogen exchange measurements in methanol. The two alamethicin simulations rapidly converged to a persistent hydrogen bond pattern with a high level of 3(10) hydrogen bonding involving the amide NH's of residues 3, 4, 9, 15, and 18. The 3(10) hydrogen bonds stabilizing amide NH's of residues C-terminal to P2 and P14 were previously proposed to explain their high amide exchange stabilities. The absence, or low levels of 3(10) hydrogen bonds at the N-terminus or for A15 NH, respectively, in the melittin simulations, is also consistent with interpretations from amide exchange analysis. Perturbation of helical hydrogen bonding in the residues before P14 (Aib10-P14, alamethicin; T11-P14, melittin) was characterized in both peptides by variable hydrogen bond patterns that included pi and gamma hydrogen bonds. The general agreement in hydrogen bond patterns determined in the simulations and from spectroscopic analysis indicates that with suitable conditions (including solvent composition and counterions where required), local hydrogen-bonded secondary structure in helical peptides may be predicted from dynamics simulations from alpha-helical starting structures. Each peptide, particularly alamethicin, underwent some large amplitude structural fluctuations in which several hydrogen bonds were cooperatively broken. The recovery of the persistent hydrogen bonding patterns after these fluctuations demonstrates the stability of intramolecular hydrogen-bonded secondary structure in methanol (consistent with spectroscopic observations), and is promising for simulations on extended timescales to characterize the nature of the backbone fluctuations that underlie amide exchange from isolated helical polypeptides.

Alamethicin↗

PubMed1998

X-ray diffuse scattering and rigid-body motion in crystalline lysozyme probed by molecular dynamics simulation.

Rigid-body motions are determined from a 1 ns molecular dynamics simulation of the unit cell of orthorhombic hen egg-white lysozyme and their contribution to X-ray diffuse scattering intensities are examined. Using a dynamical cluster technique, groups of backbone atoms that move as approximately rigid bodies are derived from the intramolecular interatomic fluctuation matrix. These groups tend to be local in the sequence or connected by disulphide bonds, and contain on average five residues each, X-ray diffuse scattering patterns, which are sensitive to collective motions, are calculated from the full simulation trajectory (including all the protein degrees of freedom). The results reproduce the main features of the experimental scattering. Diffuse scattering is also calculated from fitted trajectories of the rigid bodies. The full simulation diffuse scattering and atomic displacements are found to be well reproduced by a model in which the backbone atoms form the rigid groups determined using the dynamical cluster technique and the individual side-chains behave as separate rigid bodies: the resulting R-factor with the full simulation scattering is 5%. Quantitatively poorer agreement is obtained from trajectories in which the secondary structural elements of the protein are considered rigid. Rigid whole-molecule and domain motions make only minor contributions to the protein atom displacements. Finally, correlations in the interatomic fluctuations are examined directly using a canonical method.

Computer Simulation↗

PubMed1993

Molecular dynamics simulations of B-DNA: an analysis of the role of initial molecular configuration, randomly assigned velocity distribution, long integration times, and nonconstrained termini.

Molecular dynamics simulations of three DNA sequences using the AMBER 3.0 force field were performed with implicit inclusion of water through a distance-dependent dielectric constant and solvated counterions. Simulations of the self-complementary DNA dodecamer d(CGCGAATTCGCG) were started from a regular B-DNA structure and the x-ray single crystal B-DNA structure. Although mean convergence during the 89-ps calculation was confirmed, localized differences in backbone torsionals and base-pair helicoidals were observed. A nanosecond simulation of the nonself-complementary 14 base-pair DNA d(GGCGGAATTGGCGG) indicates that most structural parameters stabilize within the first 100-200 ps, while isolated features show low-frequency oscillations throughout the calculation. The lack of harmonic constraints on the ends of the molecules was shown not to perturb the structural dynamics of the internal oligonucleotide beyond the external 2 base pairs. Comparison of three simulations of the nonself-complementary 14 base-pair DNA d(GGCGAAATTCGCGG), identical in all respects other than the assignment of initial Maxwellian atomic velocity distributions, revealed the inherent systematic variability. The three calculations result in nearly superimposable global structures, with localized variations in torsionals and helicoidals. Our results provide a basis for performing a comparative analysis of the effect of DNA sequence on localized structure.

Base Sequence↗

PubMed2002

Ten-nanosecond molecular dynamics simulation of the motions of the horse liver alcohol dehydrogenase.PhCH2O- complex.

Molecular dynamics simulations have been carried out for a period of 10 ns with the dimeric enzyme horse liver alcohol dehydrogenase (HLADH) present as the reactive complex HLADH.NAD+. PhCH2O-. Cross-correlation analysis of the trajectory was carried out with the latter from 500 ps to 10 ns. The resulting cross-correlation map allowed the identification of the correlated and anticorrelated motions, which involve the entire protein. Anticorrelated and correlated motions are carried into the active site-aligned residues.

Alcohol Dehydrogenase↗

PubMed1995

NMR cross-relaxation investigated by molecular dynamics simulation: a case study of ubiquitin in solution.

A one nanosecond molecular dynamics simulation of ubiquitin in solution has been used for the calculation of the total dipolar, the radial and the reorientational correlation functions of 174 interproton NOEs and the 76 peptide chain NH vectors. The NOEs have been classified according to the structural elements they are associated with. Using multiexponential fits of the raw data spectral densities and cross-relaxation rate constants have been determined. Statistical distributions of correlation function parameters are given. On the basis of these data the assumptions underlying the standard method for distance measurement using NOE enhancements have been scrutinized. The separability of elongation and reorientation is verified for the vast majority of NOEs, but the rigid-body assumption is not supported by the simulation results. Relying on a spectral density expression that neither makes use of the product approximation nor neglects spatially restricted motion, a "bias-free" (with regard to molecular motion) distance measurement method is suggested and compared with the standard method. Errors in distances up to 24% and 50% occur due to the neglect of the dispersion of order parameters and correlation times, respectively. The preconditions for a class-specific calibration method have been investigated. Within the framework of the product approximation a method for decomposing the total cross-relaxation rate constant into contributions from radial and angular motion has been developed and applied. In several cases distance fluctuation contributes significantly to cross-relaxation with both amplitude and time behaviour.

Animals↗