Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Molecular Dynamic simulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
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↗
PubMed2004

Investigation of vapor-deposited amorphous ice and irradiated ice by molecular dynamics simulation.

With the purpose of clarifying a number of points raised in the experimental literature, we investigate by molecular dynamics simulation the thermodynamics, the structure and the vibrational properties of vapor-deposited amorphous ice (ASW) as well as the phase transformations experienced by crystalline and vitreous ice under ion bombardment. Concerning ASW, we have shown that by changing the conditions of the deposition process, it is possible to form either a nonmicroporous amorphous deposit whose density (approximately 1.0 g/cm3) is essentially invariant with the temperature of deposition, or a microporous sample whose density varies drastically upon temperature annealing. We find that ASW is energetically different from glassy water except at the glass transition temperature and above. Moreover, the molecular dynamics simulation shows no evidence for the formation of a high-density phase when depositing water molecules at very low temperature. In order to model the processing of interstellar ices by cosmic ray protons and heavy ions coming from the magnetospheric radiation environment around the giant planets, we bombarded samples of vitreous ice and cubic ice with 35 eV water molecules. After irradiation the recovered samples were found to be densified, the lower the temperature, the higher the density of the recovered sample. The analysis of the structure and vibrational properties of this new high-density phase of amorphous ice shows a close relationship with those of high-density amorphous ice obtained by pressure-induced amorphization.

Journal Article↗
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↗
PubMed2005

Molecular-dynamics simulation of crystallization in helical polymers.

The molecular mechanism of crystallization in helical polymers is a fascinating but very difficult subject of research. We here report our recent efforts toward better understanding of the crystallization in helical polymers by use of molecular-dynamics simulation. With straightforward approaches to the problem being quite difficult, we adopt a different strategy of categorizing the helical polymers into two distinct types: one type is a simple bare helix which is essentially made of backbone atomic groups only and has smoother molecular contours, and the other is a more general helix having large side groups that would considerably hamper molecular motion and crystallization. Both types of helical polymers are here constructed by use of the united atom model, but they show quite distinct crystallization behavior; the crystallization of the former-type polymer is rather fast, while that of the latter-type polymer is extremely slow. We find that the bare helix, when rapidly cooled in free three-dimensional space, freezes into partially ordered state with limited intramolecular and intermolecular orders, and that remarkable improvement of order and growth of an ordered chain-folded crystallite occurs by very long-time annealing of the partially ordered state around the apparent freezing temperature. We also study crystallization of the bare helix upon a growth surface; the crystallization in this case proceeds much faster through highly cooperative process of the intermolecular and the intramolecular degrees of freedom. On the other hand, crystallization of the realistic model of isotactic polypropylene (iPP) having pendant methylene groups is found to be extremely sluggish. By restricting the spatial dimension of the system thereby fully disentangling the chain, we observe that the molecule of iPP crystallizes very quickly onto the crystal substrate made of the same iPP chain. Quite remarkable is that the molecule of iPP strictly recognizes the helical sense of the substrate chain and efficiently selects its chirality during crystallization.

Journal Article↗
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↗
PubMed2005

Molecular dynamics simulations of proteins in lipid bilayers.

With recent advances in X-ray crystallography of membrane proteins promising many new high-resolution structures, molecular dynamics simulations will become increasingly valuable for understanding membrane protein function, as they can reveal the dynamic behavior concealed in the static structures. Dramatic increases in computational power, in synergy with more efficient computational methodologies, now allow us to carry out molecular dynamics simulations of any structurally known membrane protein in its native environment, covering timescales of up to 0.1 micros. At the frontiers of membrane protein simulations are ion channels, aquaporins, passive and active transporters, and bioenergetic proteins.

Computer Simulation↗
PubMed2006

Molecular dynamics simulations of SOPS and sphingomyelin bilayers containing cholesterol.

We performed a molecular dynamics simulation of an asymmetric bilayer that contained different lipid mixtures in its outer and inner leaflets. The outer leaflet contained a mixture of sphingomyelin (SM) with cholesterol and the inner leaflet a mixture of stearoyl-oleoyl-phosphatidylserine (SOPS) with cholesterol. For comparison purposes, we also performed two simulations on symmetric bilayers: the first simulation was performed on a bilayer containing a binary mixture of SOPS with cholesterol; the second contained a mixture of SM with cholesterol. We studied the hydrogen-bonding network of the bilayers in our simulations and the difference in the network properties in the monolayers either with SM or SOPS. We observed that in the asymmetric bilayer the properties of monolayers were the same as in the corresponding monolayers in the symmetric bilayers.

Cholesterol↗
PubMed2000

A molecular dynamics simulation study of coaxial stacking in RNA.

We report on unrestrained molecular dynamics simulations of an RNA tetramer binding to a tetra-nucleotide overhang at the 5'-end of an RNA hairpin (nicked structure) and of the corresponding continuous hairpin with Na+ as counterions. The simulations lead to stable structures and in this way a structural model for the coaxially stacked RNA hairpin is generated. The stacking interface in the coaxially stacked nicked hairpin structure is characterized by a reduced twist and shift and a slightly increased propeller twist as compared to the continuous system. This leads to an increased overlap between C22 and G23 in the stacking interface of the nicked structure. In the simulations the continuous RNA hairpin has an almost straight helical axis. On the other hand, the corresponding axis for the nicked structure exhibits a marked kink of 39 degrees. The stacking interface exhibits no increased flexibility as compared to the corresponding base pair step in the continuous structure.

Base Sequence↗
PubMed2002

Molecular dynamics simulations of calcium-free calmodulin in solution.

A 4-ns molecular dynamics simulation of calcium-free calmodulin in solution has been performed, using Ewald summation to treat electrostatic interactions. Our simulation results were mostly consistent with solution experimental studies, including NMR, fluorescence and x-ray scattering. The secondary structures within the N- and C-terminal domains were conserved in the simulation, with trajectory structures similar to the NMR-derived model structure 1CFD. However, the relative orientations of the domains, for which there are no NMR restraints, differed in details between the simulation and the 1CFD model. The most interesting information provided by the simulations is that the dynamics of calcium-free calmodulin in solution is dominated by slow rigid body reorientations of the domains. The interdomain distance fluctuated between 29 and 39 A, and interdomain orientation angle, defined as the pseudo-dihedral formed by the four calcium binding sites, varied between -2 degrees and 108 degrees. Similarly, the domain linker region also exhibited significant fluctuations, with its length varying in the 34-45 A range and its bend angle in the 10-100 degrees range. The simulations are in accord with fluorescence results suggesting that calcium-free calmodulin is more compact and more flexible than the calcium activated form. Surprisingly, quite similar solvent accessibilities of the hydrophobic patches were seen in the calcium-free trajectory described in this work and previously generated calcium-loaded calmodulin simulations. Thus, our simulations suggest a reexamination of the standard model of the structural change of calmodulin upon calcium binding, involving exposure of the hydrophobic patches to solvent.

Biophysical Phenomena↗
PubMed1992

A molecular dynamics simulation of bacteriophage T4 lysozyme.

An analysis of a 400 ps molecular dynamics simulation of the 164 amino acid enzyme T4 lysozyme is presented. The simulation was carried out with all hydrogen atoms modeled explicitly, the inclusion of all 152 crystallographic waters and at a temperature of 300 K. Temporal analysis of the trajectory versus energy, hydrogen bond stability, r.m.s. deviation from the starting crystal structure and radius of gyration, demonstrates that the simulation was both stable and representative of the average experimental structure. Average structural properties were calculated from the enzyme trajectory and compared with the crystal structure. The mean value of the C alpha displacements of the average simulated structure from the X-ray structure was 1.1 +/- 0.1 A; differences of the backbone phi and psi angles between the average simulated structure and the crystal structure were also examined. Thermal-B factors were calculated from the simulation for heavy and backbone atoms and both were in good agreement with experimental values. Relationships between protein secondary structure elements and internal motions were studied by examining the positional fluctuations of individual helix, sheet and turn structures. The structural integrity in the secondary structure units was preserved throughout the simulation; however, the A helix did show some unusually high atomic fluctuations. The largest backbone atom r.m.s. fluctuations were found in non-secondary structure regions; similar results were observed for r.m.s. fluctuations of non-secondary structure phi and psi angles. In general, the calculated values of r.m.s. fluctuations were quite small for the secondary structure elements. In contrast, surface loops and turns exhibited much larger values, being able to sample larger regions of conformational space. The C alpha difference distance matrix and super-positioning analyses comparing the X-ray structure with the average dynamics structure suggest that a 'hinge-bending' motion occurs between the N- and C-terminal domains.

Bacteriophage T4↗
PubMed1990

Molecular dynamics simulation of papain-E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine) complex.

To investigate the possible binding mode of E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine), a potent cysteine protease inhibitor, to papain active site, molecular dynamics simulations were applied to two complex forms: R- and S- configurational forms of E-64 C2 atom for the covalent bond formation with the papain Cys-25 SH group. The tertiary structures of the papain-E-64 complexes were built by visual interactive modelling and the energy minimization technique, and were subjected to the dynamics simulations of 10 ps. Although no significant difference was observed between the potential energies of energy-minimized R- and S-complex forms, the molecular dynamics simulations suggested that the hydrogen bonding mode of the former form is more advantageous than that of the latter one. Comparing with the hydrogen bonds observed in the papain-E-64 complex crystal, it could be concluded that the present molecular dynamics simulation reflects well the three-dimensional structure concerning the interaction of E-64 with the papain active site. The conformational characteristics of E-64 and its possible interaction mode with papain were also discussed.

Computer Simulation↗
PubMed1992

Molecular dynamics simulation of solvated protein at high pressure.

We have completed a molecular dynamics simulation of protein (bovine pancreatic trypsin inhibitor, BPTI) in solution at high pressure (10 kbar). The structural and energetic effects of the application of high pressure to solvated protein are analyzed by comparing the results of the high-pressure simulation with a corresponding simulation at low pressure. The volume of the simulation cell containing one protein molecule plus 2943 water molecules decreases by 24.7% at high pressure. This corresponds to a compressibility for the protein solution of beta = 1.8 x 10(-2) kbar-1. The compressibility of the protein is estimated to be about one-tenth that of bulk water, while the protein hydration layer water is found to have a greater compressibility as compared to the bulk, especially for water associated with hydrophobic groups. The radius of gyration of BPTI decreases by 2% and there is a one third decrease in the protein backbone atomic fluctuations at high pressure. We have analyzed pressure effects on the hydration energy of the protein. The total hydration energy is slightly (4%) more favorable at high pressure even though the surface accessibility of the protein has decreased by a corresponding amount. Large pressure-induced changes in the structure of the hydration shell are observed. Overall, the solvation shell waters appear more ordered at high pressure; the pressure-induced ordering is greatest for nonpolar surface groups. We do not observe evidence of pressure-induced unfolding of the protein over the 100-ps duration of the high-pressure simulation. This is consistent with the results of high-pressure optical experiments on BPTI.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗