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At least 37 records · Page 2Linked to original sources
PubMed2001

Exploration of partially unfolded states of human alpha-lactalbumin by molecular dynamics simulation.

Molecular dynamics simulations are used to probe the properties of non-native states of the protein human alpha-lactalbumin (human alpha-LA) with a detailed atomistic model in an implicit aqueous solvent environment. To sample the conformational space, a biasing force is introduced that increases the radius of gyration relative to the native state and generates a large number of low-energy conformers that differ in terms of their root-mean-square deviation, for a given radius of gyration. The resulting structures are relaxed by unbiased simulations and used as models of the molten globule and partly denatured states of human alpha-LA, based on measured radii of gyration obtained from nuclear magnetic resonance experiments. The ensembles of structures agree in their overall properties with experimental data available for the human alpha-LA molten globule and its more denatured states. In particular, the simulation results show that the native-like fold of the alpha-domain is preserved in the molten globule. Further, a considerable proportion of the antiparallel beta-strand in the beta-domain are present. This indicates that the lack of hydrogen exchange protection found experimentally for the beta-domain is due to rearrangement of the beta-sheet involving transient populations of non-native beta-structures. The simulations also provide details concerning the ensemble of structures that contribute as the molten globule unfolds and shows, in accord with experimental data, that unfolding is not cooperative; i.e. the various structural elements do not unfold simultaneously.

Binding Sites↗
PubMed2001

GD1a in phospholipid bilayer: a molecular dynamics simulation.

Molecular dynamics simulation of ganglioside GD1a attached to the upper layer of a fully hydrated lipid bilayer of dimyristoyl phosphatidyl choline (DMPC) at room temperature under periodic boundary conditions was performed. The time average conformation of GD1a reveals that the terminal sialic acid is more exposed into the solvent than the internal branched one. Many interresidual contacts between N-acetyl galactosamine-internal branched sialic acid; external Gal-external sialic acid; N-acetyl galactosamine-internal gal are also observed. The conformation of the GD1-hexasaccharide is stabilized by a number of intra molecular hydrogen bonds that were previously observed experimentally. The simulation results indicate that the presence of a single GD1a molecule has local effects on the bilayer. A local disorder in the arrangement of the acyl chains as well as the head groups is evident in the upper layer due to the presence of GD1a.

Acetylgalactosamine↗
PubMed1998

Lipid properties and the orientation of aromatic residues in OmpF, influenza M2, and alamethicin systems: molecular dynamics simulations.

Molecular dynamics simulations allow a direct study of the structure and dynamics of membrane proteins and lipids. We describe the behavior of aromatic residues and lipid properties in POPE and POPC bilayer models with the Escherichia coli OmpF trimer, single alamethicin and Influenza M2 helices, 4-helix M2 bundles, and two alamethicin 6-helix channel models. The total simulation time is over 24 ns, of systems containing solvent, protein, and between 104 and 318 lipids. Various types of adjustment between lipids and proteins occur, depending on the size of the protein and the degree of hydrophobic mismatch between lipid and protein. Single helices cause little measurable effect on nearby lipids whereas the 4-helix bundles, 6-helix channel models, and OmpF cause a significant lowering of order parameters in nearby lipid chains, an increased difference between odd and even chain dihedrals in the magnitude of the trans dihedral fractions and dihedral transition rates, and in most cases a decreased gauche population and a decrease in bilayer thickness. An increased tilt of the lipid chains near the proteins can account for most of the observed decrease in order parameters. The orientation of tryptophans and tyrosines on the outside of the proteins is determined by packing at the protein exterior and non-specific hydrogen bonding with lipids and solvent. The tyrosines in the broad bands that delimit the hydrophobic exterior of OmpF show little change in orientation over one nanosecond. Their rings are oriented predominantly perpendicular to the bilayer plane, with the hydroxyl group pointing toward the lipid-water interface. Phenylalanines in OmpF, alamethicin, and Influenza M2 are more mobile and assume a variety of orientations.

Alamethicin↗
PubMed2005

Internal cavities and ligand passageways in human hemoglobin characterized by molecular dynamics simulations.

Molecular dynamics simulations of the unliganded T state of human hemoglobin showed the existence of a spontaneous, very wide cavity on the distal side of the alpha subunit. This cavity consists of three tunnels spreading from the vicinity of the iron atom (the ligand binding site) to the surface of the subunit, constituting possible passageways for the entrance of the ligand. A fourth passageway was characterized due to the trajectory of water molecules entering or leaving the heme pocket. Analogous passages were observed in the beta subunits. They all appear and disappear dynamically, although some parts of them are more persistent along the trajectories. The most persistent regions within these tunnels correspond to all the xenon docking sites of human cytoglobin and to some of those of sperm whale and horse heart myoglobins and group I truncated hemoglobins.

Binding Sites↗
PubMed2001

Structure and stability of the insulin dimer investigated by molecular dynamics simulation.

Molecular dynamics simulation indicates that the dynamical behaviour of the insulin dimer is asymmetric. Atomic level knowledge of the interaction modes and protein conformation in the solvation state identifies dynamical structures, held by hydrogen bonds that stabilize, mainly in one monomer, the interaction between the chains. Dynamic cross-correlation analysis shows that the two insulin monomers behave asymmetrically and are almost independent. Solvation energy, calculated to evaluate the contribute of each interface residue to the dimer association pattern, well compares with the experimental association state found in protein mutants indicating that this parameter is an important factor to explain the association properties of mutated insulin dimers.

Computer Simulation↗
PubMed2003

Effects of pressure on the fragile nature of fluorozirconates studied by molecular dynamics simulations.

Molecular dynamics simulations for a multicomponent zirconium fluoride, ZBEN (55ZrF(4)-17BaF(2)-5EuF(3)-23NaF) have been carried out at various temperatures and pressures including those of the molten and glassy states. The effect of pressure on the fragile nature of ZBEN was investigated. The relaxation times were calculated from the decay curves of the intermediate scattering function. The fragile nature of ZBEN was reflected by the obvious non-Arrhenius behavior in the temperature dependence of the relaxation time. The so-called "Angell plot" of the relaxation time was represented by a single curve irrespective of applied pressure; the fragile nature changes negligibly with pressure. This seems to contradict the enhancement of the connectivity of ZrF(n) polyhedra under high pressure. The origin of the pressure effects is discussed in comparison with those for molecular liquids and covalent-network glasses.

Journal Article↗
PubMed1991

Cooperative ligand reorientations in cytochrome c3: a molecular dynamics simulation.

Molecular dynamics simulations of a tetraheme cytochrome c3 were performed to investigate dynamic aspects of the motion of the axial heme iron ligands. It was found that persistent transitions between alternate axial imidazole orientations of the histidine incorporated in the CXXCH heme binding sequence occurred via correlated motions. The correlated motions involved virtually all of the atoms comprising the polypeptide backbone of the heme binding sequence as well as the histidine imidazole side-chain.

Amino Acid Sequence↗
PubMed2001

Role of the helix capping in the stability of the mouse prion (180-213) segment: investigation through molecular dynamics simulations.

Molecular dynamics simulation of the 180-213 segment, forming the B and C helices in the mouse prion protein, and of three mutants, where the capping box residues or the hydrophobic staple motif residues were selectively mutated, have been carried out. The results indicate that the wild type segment is stable over all the trajectory, whilst the mutants display different degrees of destabilization. In detail mutation of Asp202 brings to a rapid unfolding of helix C likely because of the concomitant loss of a hydrogen bond and of a negative charge able to stabilize the dipole in the first turn of the helix. A lower destabilizing effect is observed upon mutation Thr199. On the other hand mutation of Phe198 and Val203, the hydrophobic staple residues, brings to an incorrect orientation of the first helix relative to the second one due to a weakening of the hydrophobic interaction. The results confirm the importance of the presence of both motifs for the structural integrity of the isolated fragment and suggest that these residues may have a main role in the structural transition observed in the inherited human prion diseases.

Amino Acid Sequence↗
PubMed2000

Mesoscopic undulations and thickness fluctuations in lipid bilayers from molecular dynamics simulations.

Molecular dynamics simulations of fully hydrated Dipalmitoylphosphatidylcholine bilayers, extending temporal and spatial scales by almost one order of magnitude, are presented. The present work reaches system sizes of 1024 lipids and times 10-60 ns. The simulations uncover significant dynamics and fluctuations on scales of several nanoseconds, and enable direct observation and spectral decomposition of both undulatory and thickness fluctuation modes. Although the former modes are strongly damped, the latter exhibit signs of oscillatory behavior. From this, it has been possible to calculate mesoscopic continuum properties in good agreement with experimental values. A bending modulus of 4 x 10(-20) J, bilayer area compressibility of 250-300 mN/m, and mode relaxation times in the nanosecond range are obtained. The theory of undulatory motions is revised and further extended to cover thickness fluctuations. Finally, it is proposed that thickness fluctuations is the explanation to the observed system-size dependence of equilibrium-projected area per lipid.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Role of water on unfolding kinetics of helical peptides studied by molecular dynamics simulations.

Molecular dynamics simulations have been carried out with four polypeptides, Ala13, Val(13), Ser13, and Ala4Gly5Ala4, in vacuo and with explicit hydration. The unfolding of the polypeptides, which are initially fully alpha-helix in conformation, has been monitored during trajectories of 0.3 ns at 350 K. A rank of Ala < Val < Ser < Gly is found in the order of increasing rate of unwinding. The unfolding of Ala13 and Val(13) is completed in hundreds of picoseconds, while that of Ser13 is about one order of magnitude faster. The helix content of the peptide containing glycine residues falls to zero within a few picoseconds. Ramachandran plots indicate quite distinct equilibrium distributions and time evolution of dihedral angles in water and in vacuum for each residue type. The unfolding of polyalanine and polyvaline helices is accelerated due to solvation. In contrast, polyserine is more stable in water compared to vacuum, because its side chains can form intramolecular hydrogen bonds with the backbone more readily in vacuum, which disrupts the helix. Distribution functions of the spatial and angular position of water molecules in the proximity of the polypeptide backbone polar groups reveal the stabilization of the coiled structures by hydration. The transition from helix to coil is characterized by the appearance of a new peak in the probability distribution at a specific location characteristic of hydrogen bond formation between water and backbone polar groups. No significant insertion of water molecules is observed at the precise onset of unwinding, while (i, i+3) hydrogen bond formation is frequently detected at the initiation of alpha-helix unwinding.

Biophysical Phenomena↗
PubMed2005

Characterization of titanium dioxide nanoparticles using molecular dynamics simulations.

Molecular dynamics simulations of titanium dioxide nanoparticles in the three commonly occurring phases (anatase, brookite, and rutile) are reported. The structural properties inferred by simulated X-ray diffraction patterns of the nanoparticles were investigated. The titanium-oxygen bond length as a function of size, phase, and temperature was determined and was found to be dependent on the coordination environment of the titanium and independent of phase and size. The equilibrium Ti-O bond length is 1.86 A for a four-coordinated titanium ion, 1.92 A for a five-coordinated titanium ion, and 1.94 A for an octahedral titanium ion. Smaller nanoparticles are characterized by a higher fraction of titanium ions that are four and five coordinated, due to the larger surface area-to-volume ratios. The surface energies for anatase, rutile, and brookite particles were reported. The surface energy of the nanoparticle increases and approaches a constant value as the particle gets bigger. The surface energies of small rutile particles are higher than that for anatase particles of a similar size, consistent with anatase being the more stable phase of nanocrystalline titanium dioxide.

Journal Article↗
PubMed2005

Structure of an associating polymer melt in a narrow slit by molecular dynamics simulation.

Molecular dynamics simulation has been used to study the equilibrium properties of a generic coarse-grained polymer melt with associating terminal groups, confined in a narrow slit by two atomically smooth walls. Simulations were carried out as a function of wall separation and attracting strength as well as polymer end-end interaction strength. We find that confinement has an important effect on the melt properties. In particular, strongly attracting walls can produce radical changes in chain conformation, the nature of the transient network, and the structure of the aggregates formed by the associating terminals.

Journal Article↗
PubMed2005

Melting of icosahedral gold nanoclusters from molecular dynamics simulations.

Molecular dynamics simulations show that gold clusters with about 600-3000 atoms crystallize into a Mackay icosahedron upon cooling from the liquid. A detailed surface analysis shows that the facets on the surface of the Mackay icosahedral gold clusters soften but do not premelt below the bulk melting temperature. This softening is found to be due to the increasing mobility of vertex and edge atoms with temperature, which leads to inter-layer and intra-layer diffusion, and a shrinkage of the average facet size, so that the average shape of the cluster is nearly spherical at melting.

Journal Article↗
PubMed2006

Evaluation of intrinsic compressibility of proteins by molecular dynamics simulation.

Molecular dynamics simulation has been performed on five native proteins in water to evaluate their intrinsic isothermal compressibilities beta(T,int). To identify physical factors contributing to protein compressibility, a general method is presented for analyzing the compressibility of mechanically inhomogeneous systems. The value of beta(T,int) varies with protein species considerably: beta-lactoglobulin (14.15 x 10(-2) GPa(-1)) is more than twice as compressible as ribonuclease A (6.77 x 10(-2) GPa(-1)). Beta-lactoglobulin and myoglobin (13.95 x 10(-2) GPa(-1)) have similar values of beta(T,int), but the mechanisms responsible for them are significantly different. The volume fluctuations of internal cavities and the magnitudes of the crosscorrelation between them are the key factors determining beta(T,int) of proteins. Though the volume fractions of internal cavity for the five studied proteins are nearly equal to one another, the mean cavity compressibilities beta(T,cav) vary considerably with protein species and range from 0.35 to 0.69 GPa(-1), which are much smaller than those of normal organic liquids such as methanol, ethanol, and benzene and close to that of glycerol (0.55 GPa(-1)), a strongly associated liquid.

Animals↗
PubMed2006

General continuum boundary conditions for miscible binary fluids from molecular dynamics simulations.

Molecular dynamics simulations are used to explore the flow behavior and diffusion of miscible fluids near solid surfaces. The solid produces deviations from bulk fluid behavior that decay over a distance of the order of the fluid correlation length. Atomistic results are mapped onto two types of continuum model: Mesoscopic models that follow this decay and conventional sharp interface boundary conditions for the stress and velocity. The atomistic results, and mesoscopic models derived from them, are consistent with the conventional Marangoni stress boundary condition. However, there are deviations from the conventional Navier boundary condition that states that the slip velocity between wall and fluid is proportional to the strain rate. A general slip boundary condition is derived from the mesoscopic model that contains additional terms associated with the Marangoni stress and diffusion, and is shown to describe the atomistic simulations. The additional terms lead to strong flows when there is a concentration gradient. The potential for using this effect to make a nanomotor or pump is evaluated.

Journal Article↗
PubMed1993

Nonexponential relaxation after ligand dissociation from myoglobin: a molecular dynamics simulation.

Molecular dynamics simulations of myoglobin after ligand photodissociation show that the out-of-plane motion of the heme iron has a rapid subpicosecond phase followed by a slower nonexponential process involving more global protein relaxation. Individual trajectories show rather different behavior, suggesting there is an inhomogeneous component to the relaxation. The calculated time dependence of the iron motion over 100 ps is in excellent agreement with the frequency shift of band III of the heme group [see Lim, M., Jackson, T. A. & Anfinrud, P. A. (1993) Proc. Natl. Acad. Sci. USA 90, 5801-5804]. If that the barrier to rebinding depends on the out-of-plane iron position, the time dependence obtained from the simulation can explain the nonexponential room-temperature geminate recombination of NO.

Kinetics↗
PubMed1996

Glass transition in DNA from molecular dynamics simulations.

Molecular dynamics simulations of the oligonucleotide duplex d(CGCGCG)2 in aqueous solution are used to investigate the glass transition phenomenon. The simulations were performed at temperatures in the 20 K to 340 K range. The mean square atomic fluctuations showed that the behavior of the oligonucleotide duplex was harmonic at low temperatures. A glass transition temperature at 223 K to 234 K was inferred for the oligonucleotide duplex, which is in agreement with experimental observations. The largest number of hydrogen bounds between the polar atoms of the oligonucleotide duplex and the water molecules was obtained at the glass transition temperature. With increasing temperature we observed a decrease in the average lifetime of the hydrogen bonds to water molecules.

Base Sequence↗
PubMed2006

Structure, dynamics, and elasticity of free 16s rRNA helix 44 studied by molecular dynamics simulations.

Molecular dynamics (MD) simulations were employed to investigate the structure, dynamics, and local base-pair step deformability of the free 16S ribosomal helix 44 from Thermus thermophilus and of a canonical A-RNA double helix. While helix 44 is bent in the crystal structure of the small ribosomal subunit, the simulated helix 44 is intrinsically straight. It shows, however, substantial instantaneous bends that are isotropic. The spontaneous motions seen in simulations achieve large degrees of bending seen in the X-ray structure and would be entirely sufficient to allow the dynamics of the upper part of helix 44 evidenced by cryo-electron microscopic studies. Analysis of local base-pair step deformability reveals a patch of flexible steps in the upper part of helix 44 and in the area proximal to the bulge bases, suggesting that the upper part of helix 44 has enhanced flexibility. The simulations identify two conformational substates of the second bulge area (bottom part of the helix) with distinct base pairing. In agreement with nuclear magnetic resonance (NMR) and X-ray studies, a flipped out conformational substate of conserved 1492A is seen in the first bulge area. Molecular dynamics (MD) simulations reveal a number of reversible alpha-gamma backbone flips that correspond to transitions between two known A-RNA backbone families. The flipped substates do not cumulate along the trajectory and lead to a modest transient reduction of helical twist with no significant influence on the overall geometry of the duplexes. Despite their considerable flexibility, the simulated structures are very stable with no indication of substantial force field inaccuracies.

Base Pairing↗