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Results for “Molecular Dynamic simulation”

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At least 307 records · Page 17Linked to original sources

PubMed2006

Nonlinear ionic conductivity of lithium silicate glass studied via molecular dynamics simulations.

Nonlinear ionic conductivity effects are studied via molecular dynamics simulations. We present numerical results for the field dependence of the current density as well as the second moment of the ion displacements. Furthermore we check whether structural changes occur upon application of strong electric fields. We obtain a complex picture of the field-dependent ion dynamics of a disordered system that is beyond simple model descriptions.

Journal Article↗

PubMed2002

Molecular dynamics simulation of GM1 in phospholipid bilayer.

We report molecular dynamics simulation of fully hydrated lipid bilayer of dimyristoyl phosphatidyl choline (DMPC) at room temperature with ganglioside GM1 attached to it in the upper layer under periodic boundary conditions. The simulation results indicate that the presence of a single GM1 molecule has local effects on the bilayer. Three sugar residues (GalNAc-Gal-Glc) of the pentasaccharide head group of GM1 remain on the lipid surface where as the NeuNAc residue extends out in the aqueous layer. The radial distribution functions suggest ordering of water molecules near the glycerol and carboxyl group of the sialic acid in the upper layer. One of the ceramide chains of GM1, the sphingosine chain, folds up and is stacked under the sugar residues lying on the surface. The other ceramide chain is inserted into the lipid bilayer. The arrangement of the polar head group as well as the acyl chains of the lipids which are immediate neighbours of the GM1 are modified compared to the non-neighbour ones and others at the lower layer. The time average conformation of GM1-pentasaccharide is stabilized by a number of inter residue hydrogen bonds that were observed experimentally. The trajectory average conformation of GM1-pentasaccharide was docked on to the cholera toxin molecule and the minimized complex reveals alternative binding modes between the toxin and the GM1-pentasaccharide moiety. The results of these simulation studies might help to understand the structure and nature of the effects of GM1 on the membrane at atomic resolution.

Cholera Toxin↗

PubMed2003

Effects of asymmetric salt and a cylindrical macroion on charge inversion: electrophoresis by molecular dynamics simulations.

The charge inversion phenomenon is studied by molecular dynamics simulations, focusing on size and valence asymmetric salts, and a threshold of surface charge density for charge inversion. The charge inversion criteria by the electrophoretic mobility and the radial distribution functions of ions coincide except around the charge inversion threshold. The reversed electrophoretic mobility increases with the ratio of coion to counterion radii, a(-)/a(+), while it decreases with the ratio of coion to counterion valences, Z(-)/Z(+). The monovalent salt enhances charge inversion of a strongly charged macroion at small salt ionic strength, while it reduces reversed mobility otherwise. A cylindrical macroion is more persistent to monovalent salt than a spherical macroion of the same radius and surface charge density.

Journal Article↗

PubMed2006

Glass transition in 1,4-polybutadiene: Mode-coupling theory analysis of molecular dynamics simulations using a chemically realistic model.

We present molecular dynamics simulations of the glass transition in a chemically realistic model of 1,4-polybutadiene (PBD). Around 40 K above the calorimetric glass transition of this polymer the simulations reveal a well-developed two-stage relaxation of all correlation functions. We have analyzed the time-scale separation between vibrational degrees of freedom (subpicosecond dynamics) and the alpha relaxation behavior (nanosecond to microsecond dynamics) using the predictions of mode-coupling theory (MCT). Our value for the mode-coupling critical temperature Tc agrees perfectly with prior experimental estimates for PBD. The predictions of MCT for the scaling behavior of the so-called beta relaxation, the plateau regime separating vibrational dynamics and the alpha relaxation, are well fulfilled. Furthermore, we are able to derive a consistent set of MCT exponents, completely characterizing the scaling behavior of relaxation processes in the vicinity of Tc. For the temperature dependence of the alpha relaxation we find deviations from MCT predictions which we trace to the influence of torsional barriers on the atomic motions.

Journal Article↗

PubMed1997

Classical molecular dynamics simulation of the photoinduced electron transfer dynamics of plastocyanin.

Classical molecular dynamics simulations are used to investigate the nuclear motions associated with photoinduced electron transfer in plastocyanin. The blue copper protein is modeled using a molecular mechanics potential; potential parameters for the copper-protein interactions are determined using an x-ray crystallographic structure and absorption and resonance Raman spectra. Molecular dynamics simulations yield a variety of information about the ground (oxidized) and optically excited (charge-transfer) states: 1) The probability distribution of the potential difference between the states, which is used to determine the coordinate and energy displacements, places the states well within the Marcus inverted region. 2) The two-time autocorrelation function of the difference potential in the ground state and the average of the difference potential after instantaneous excitation to the excited state are very similar (confirming linear response in this system); their decay indicates that vibrational relaxation occurs in about 1 ps in both states. 3) The spectral densities of various internal coordinates begin to identify the vibrations that affect the optical transition; the spectral density of the difference potential correlation function should also prove useful in quantum simulations of the back electron transfer. 4) Correlation functions of the protein atomic motions with the difference potential show that the nuclear motions are correlated over a distance of more than 20 A, especially along proposed electron transport paths.

Binding Sites↗

PubMed2006

Phenol-benzene complexation dynamics: quantum chemistry calculation, molecular dynamics simulations, and two dimensional IR spectroscopy.

Molecular dynamics (MD) simulations and quantum mechanical electronic structure calculations are used to investigate the nature and dynamics of the phenol-benzene complex in the mixed solvent, benzene/CCl4. Under thermal equilibrium conditions, the complexes are continuously dissociating and forming. The MD simulations are used to calculate the experimental observables related to the phenol hydroxyl stretching mode, i.e., the two dimensional infrared vibrational echo spectrum as a function of time, which directly displays the formation and dissociation of the complex through the growth of off-diagonal peaks, and the linear absorption spectrum, which displays two hydroxyl stretch peaks, one for the complex and one for the free phenol. The results of the simulations are compared to previously reported experimental data and are found to be in quite reasonable agreement. The electronic structure calculations show that the complex is T shaped. The classical potential used for the phenol-benzene interaction in the MD simulations is in good accord with the highest level of the electronic structure calculations. A variety of other features is extracted from the simulations including the relationship between the structure and the projection of the electric field on the hydroxyl group. The fluctuating electric field is used to determine the hydroxyl stretch frequency-frequency correlation function (FFCF). The simulations are also used to examine the number distribution of benzene and CCl4 molecules in the first solvent shell around the phenol. It is found that the distribution is not that of the solvent mole fraction of benzene. There are substantial probabilities of finding a phenol in either a pure benzene environment or a pure CCl4 environment. A conjecture is made that relates the FFCF to the local number of benzene molecules in phenol's first solvent shell.

Benzene↗

PubMed2006

Coarse-grained molecular dynamics simulations of membrane proteins and peptides.

Molecular dynamics (MD) simulations provide a valuable approach to the dynamics, structure, and stability of membrane-protein systems. Coarse-grained (CG) models, in which small groups of atoms are treated as single particles, enable extended (>100 ns) timescales to be addressed. In this study, we explore how CG-MD methods that have been developed for detergents and lipids may be extended to membrane proteins. In particular, CG-MD simulations of a number of membrane peptides and proteins are used to characterize their interactions with lipid bilayers. CG-MD is used to simulate the insertion of synthetic model membrane peptides (WALPs and LS3) into a lipid (PC) bilayer. WALP peptides insert in a transmembrane orientation, whilst the LS3 peptide adopts an interfacial location, both in agreement with experimental biophysical data. This approach is extended to a transmembrane fragment of the Vpu protein from HIV-1, and to the coat protein from fd phage. Again, simulated protein/membrane interactions are in good agreement with solid state NMR data for these proteins. CG-MD has also been applied to an M3-M4 fragment from the CFTR protein. Simulations of CFTR M3-M4 in a detergent micelle reveal formation of an alpha-helical hairpin, consistent with a variety of biophysical data. In an I231D mutant, the M3-M4 hairpin is additionally stabilized via an inter-helix Q207/D231 interaction. Finally, CG-MD simulations are extended to a more complex membrane protein, the bacterial sugar transporter LacY. Comparison of a 200 ns CG-MD simulation of LacY in a DPPC bilayer with a 50 ns atomistic simulation of the same protein in a DMPC bilayer shows that the two methods yield comparable predictions of lipid-protein interactions. Taken together, these results demonstrate the utility of CG-MD simulations for studies of membrane/protein interactions.

Amino Acid Sequence↗

PubMed2002

Folded conformation of an immunostimulating tetrapeptide rigin: high temperature molecular dynamics simulation study.

Employing high temperature quenched molecular dynamics (QMD) stimulations the conformational energy space of an immunostimulating tetrapeptide rigin: H-Gly341-Gln-Pro-Arg344-OH, is explored. Using distance dependent dielectric (epsilon =r(ij)) 31 different low energy starting structures with identical sequence were computed for their conformational preferences. According to the hypothesis of O'Connors et al. [J. Med. Chem. 35 (1992), 2870], 83 low-energy conformers resulted from unrestrained molecular dynamics (MD) simulations, could be classified into two energy minimized families: A and B, comprised of 64 (Pro C(gamma)-endo orientation) and 19 (Pro C(gamma)-exo orientation) structures, respectively. An examination of these families revealed the existence of a remarkably similar folded backbone conformation: torsion angles being phi(i+1) approximately -65 degrees, psi(i+1) approximately -65 degrees, phi(i+2) approximately -65 degrees, psi(i+2) approximately -60 degrees, characterizing a distorted type III beta-turn structure across the central Gln-Pro segment. The folded conformation of rigin is devoid of a classical 1 <-- 4 intra-molecular hydrogen bond nevertheless, the conformation is stabilized by an effective 'salt-bridge', i.e., Gly H(3)N(+)...C(alpha)OO(-) Arg interaction. Surprisingly, in both the families the unusual folded side-chain dispositions of the Gln residue favor the formation of a unique intra-residue 'main-chain to side-chain' H-bond, i.e., N(alpha)-H...N(epsilon) interaction, encompassing a seven-membered ring motif. The conformational attributes may be valuable in de novo construction of structure-based drug candidates having sufficient stimulating activity.

Adjuvants, Immunologic↗

PubMed2001

Molecular dynamics simulation of class 3 aldehyde dehydrogenase.

Molecular dynamics (MD) simulation of the rat class 3 aldehyde dehydrogenase (ALDH) with nicotinamide dinucleotide (NAD) cofactors and explicit water molecules are reported. Our results demonstrate that MD simulation using the latest methodologies can maintain the crystal structure of the enzyme, as well as closely reproduce the short timescale dynamics of the enzyme. Furthermore, the examination of the distance between the nucleophilic Cys-243 and the NAD cofactor reveal important fluctuations that could be linked to ALDH catalysis. Finally, our quantum mechanical model of benzaldehyde in the active site of ALDH demonstrates that the enzyme requires only minor conformational changes to be poised for nucleophilic attack on the substrate.

Aldehyde Dehydrogenase↗

PubMed2001

Folding study of an Aib-rich peptide in DMSO by molecular dynamics simulations.

To evaluate the ability of molecular dynamics (MD) simulations using atomic force-fields to correctly predict stable folded conformations of a peptide in solution, we show results from MD simulations of the reversible folding of an octapeptide rich in alpha-aminoisobutyric acid (2-amino-2-methyl-propanoic acid, Aib) solvated in di-methyl-sulfoxide (DMSO). This solvent generally prevents the formation of secondary structure, whereas Aib-rich peptides show a high propensity to form secondary structural elements, in particular 3(10)- and alpha-helical structures. Aib is, moreover, achiral, so that Aib-rich peptides can form left- or right-handed helices depending on the overall composition of the peptide, the temperature, and the solvation conditions. This makes the system an interesting case to study the ensembles of peptide conformations as a function of temperature by MD simulation. Simulations involving the folding and unfolding of the peptide were performed starting from two initial structures, a right-handed alpha-helical structure and an extended structure, at three temperatures, 298 K, 340 K, and 380 K, and the results are compared with experimental nuclear magnetic resonance (NMR) data measured at 298 K and 340 K. The simulations generally reproduce the available experimental nuclear Overhauser effect (NOE) data, even when a wide range of conformations is sampled at each temperature. The importance of adequate statistical sampling in order to reliably interpret the experimental data is discussed.

Dimethyl Sulfoxide↗

PubMed2001

Isobaric molecular dynamics simulations of hard sphere systems.

We describe an implementation of the Andersen algorithm for simulating the molecular dynamics in the isobaric isoenthalpic (NPH) ensemble for the hard sphere potential. The work is based on the adaptation of the Andersen algorithm to hard spheres by de Smedt et al. For a hard sphere system in the NPH ensemble, the particle velocities are not constant between collisions and we describe an efficient method for handling this part of the dynamics. The method is extended to give an NPT ensemble simulation of hard sphere systems by applying an ad hoc rescaling of the velocities. The accuracy of the algorithms is tested by comparison with traditional NVE simulation results for the structural, thermodynamic, and transport properties.

Journal Article↗

PubMed2002

New approach to free energy of solvation applying continuum models to molecular dynamics simulation.

A new approach to the calculation of the free energy of solvation from trajectories obtained by molecular dynamics simulation is presented. The free energy of solvation is computed as the sum of three contributions originated at the cavitation of the solute by the solvent, the solute-solvent nonpolar (repulsion and dispersion) interactions, and the electrostatic solvation of the solute. The electrostatic term is calculated based on ideas developed for the broadly used continuum models, the cavitational contribution from the excluded volume by the Claverie-Pierotti model, and the Van der Waals term directly from the molecular dynamics simulation. The proposed model is tested for diluted aqueous solutions of simple molecules containing a variety of chemically important functions: methanol, methylamine, water, methanethiol, and dichloromethane. These solutions were treated by molecular dynamics simulations using SPC/E water and the OPLS force field for the organic molecules. Obtained free energies of solvation are in very good agreement with experimental data.

Journal Article↗

PubMed2001

Model of the 3-D structure of the GLUT3 glucose transporter and molecular dynamics simulation of glucose transport.

A molecular model of the three-dimensional (3-D) structure of the glucose transport protein, GLUT3, has been derived by homology modeling. The model was built on the basis of structural data from the MscL protein, which is a mechanosensitive ion channel, and general insights from aquaporin (a water permeation pore). Structurally conserved regions were defined by amino acid sequence comparisons, optimum interconnecting loops were selected from the protein databank, and amino (N)- and carboxy (C)-terminal ends of the protein were generated as random coil structures. The model was then subjected to energy minimization and molecular dynamics simulations in the presence of bound substrate (D-glucose). In the proposed structure of GLUT3, the 12 transmembrane (TM) helices form a right-hand barrel with a central hydrophilic pore. The pore is shaped like a funnel with dimensions of approximately 5-6 A by 8 A at its narrowest point. A network of polar and aromatic amino acids line the pore region and may facilitate the movement of glucose along the channel. A putative binding site for inhibitory ligands, such as forskolin and cytochalasin B, was identified on an intracellular aspect of the protein. Molecular dynamics studies showed that changes in the tilt and flexibility of key TM helices may modulate the opening of the pore to effect glucose transport. The proposed structure of GLUT3 may prove useful in guiding future experiments aimed at more precisely defining various functional regions of the transporter and may encourage efforts to develop models of other complex membrane proteins.

Amino Acid Sequence↗

PubMed1999

Assignment of side-chain conformation using adiabatic energy mapping, free energy perturbation, and molecular dynamic simulations.

NMR spectroscopic analysis of the C-terminal Kunitz domain fragment (alpha3(VI)) from the human alpha3-chain of type VI collagen has revealed that the side chain of Trp21 exists in two unequally populated conformations. The major conformation (M) is identical to the conformation observed in the X-ray crystallographic structure, while the minor conformation (m) cannot structurally be resolved in detail by NMR due to insufficient NOE data. In the present study, we have applied: (1) rigid and adiabatic mapping, (2) free energy simulations, and (3) molecular dynamic simulations to elucidate the structure of the m conformer and to provide a possible pathway of the Trp21 side chain between the two conformers. Adiabatic energy mapping of conformations of the Trp21 side chain obtained by energy minimization identified two energy minima: One corresponding to the conformation of Trp21 observed in the X-ray crystallographic structure and solution structure of alpha3(VI) (the M conformation) and the second corresponding to the m conformation predicted by NMR spectroscopy. A transition pathway between the M and m conformation is suggested. The free-energy difference between the two conformers obtained by the thermodynamic integration method is calculated to 1.77+/-0.7 kcal/mol in favor of the M form, which is in good agreement with NMR results. Structural and dynamic properties of the major and minor conformers of the alpha3(VI) molecule were investigated by molecular dynamic. Essential dynamics analysis of the two resulting 800 ps trajectories reveals that when going from the M to the m conformation only small, localized changes in the protein structure are induced. However, notable differences are observed in the mobility of the binding loop (residues Thr13-Ile18), which is more flexible in the m conformation than in the M conformation. This suggests that the reorientation of Trp2 might influence the inhibitory activity against trypsin, despite the relative large distance between the binding loop and Trp21.

Collagen↗

PubMed1987

Lipid bilayer polypeptide interactions studied by molecular dynamics simulation.

A model membrane with a polypeptide alpha-helix inserted has been simulated by molecular dynamics at a temperature well above the gel/liquid crystalline phase transition temperature. Order parameters of the lipids and other equilibrium and dynamic quantities have been calculated. Three systems, polyglycine constrained into an alpha-helical configuration, glycophorin with similarly conformationally constrained backbone and finally glycophorin free to change its backbone conformation, have been studied. In all cases there was an ordering of the chains close to the helix. This effect was, however, much smaller for glycophorin with its rather bulky side chains than for polyglycine. The dynamics of the lipids were affected by the neighbouring helix, not drastically however. Lateral diffusion and reorientational time correlations of lipids close to the helix were slower than for the bulk ones, but not more than two or three times. Thus, we did not find any evidence of bound or frozen boundary lipids.

Glycophorins↗

PubMed2006

Kinetic insights into the role of the solvent in the polymorphism of 5-fluorouracil from molecular dynamics simulations.

We investigate the fundamental factors controlling polymorphism in 5-fluorouracil by performing molecular dynamics simulations of solutions of the compound in water, nitromethane, and wet nitromethane. Analysis of the effect of solvent on the initial aggregation of 5-fluorouracil molecules shows that the strong binding of water to the 5-fluorouracil molecule hinders the formation of the doubly hydrogen-bonded dimer and, by default, promotes close hydrophobic F...F interactions that are a feature of the unusual (Z' = 4) structure of form I. In contrast, doubly hydrogen-bonded dimers are observed to form readily in solution in dry nitromethane, consistent with the crystallization of the doubly hydrogen-bonded ribbon structure of form II from this solvent. When nitromethane is doped with water, the water forms hydrogen bonds to the solute, interfering with the formation of the doubly hydrogen-bonded dimers, which is consistent with the crystallization of form I from this hygroscopic solvent when it is not dried. Overall, the molecular dynamics simulations provide an atomistic picture of how solvent-solute interactions can significantly affect the initial association of 5-fluorouracil molecules to the extent that they determine the polymorphic outcome of the crystallization.

Antimetabolites, Antineoplastic↗

PubMed2005

[Molecular dynamics simulation of dark-adapted rhodopsin and free opsin].

Molecular dynamics simulation was carried out for the rhodopsin protein to investigate its conformational changes in respect to inclusion of 11-cis retinal chromophore. Molecular dynamics calculations were performed within the time frame 3000 ps. Totally, 3 X 10(6) configurations ofrhodopsin and free opsin were analyzed and compared. It has been shown that the 11-cis retinal rearrangement (adaptation) in opsin strongly affects the surrounding amino acid residues of protein binding pocket and the protein cytoplasmic region. The extracellular part, however, shows comparatively little changes. On basis of the simulation results obtained we propose a molecular mechanism for the rhodopsin protein function as a G-protein-coupled receptor in the state of darkness. We discuss the role of the retinal chromophore as a ligand-antagonist stabilizing the inactive conformation of rhodopsin.

Animals↗

PubMed1992

Molecular dynamics simulation in vacuo and in solution of [Aib5,6-D-Ala8] cyclolinopeptide A: a conformational and comparative study.

The conformation of a Cyclolinopeptide A analogue, c-(Pro-Pro-Phe-Phe-Aib-Aib-Ile-D-Ala-Val), has been investigated by means of molecular dynamics simulations, in various molecular environments. The molecular dynamics results are compared with that obtained for Cyclolinopeptide A and a detailed analysis of the different behaviour for the two compounds is reported. A complete analysis of hydrogen bonds is presented.

Amino Acid Sequence↗