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At least 343 records · Page 19Linked to original sources
PubMed2006

Topological and dynamical properties of Azurin anchored to a gold substrate as investigated by molecular dynamics simulation.

A classical molecular dynamics study of the electron transfer protein azurin, covalently bound to a gold substrate through its native disulphide group, is carried out at full hydration. With the aim of investigating the effects on the protein structure and dynamics as induced by the presence of an electric field, simulations are performed on neutral, positively and negatively charged substrates. A number of parameters, such as the average structure, the root mean square deviations and fluctuations, the intraprotein hydrogen bonds and solvent accessible surface of the protein, are monitored during 10 ns of run. The orientation, the height and the lateral size of the protein, with respect to the substrate are evaluated and compared with the experimental data obtained by scanning probe nanoscopies. The electron transfer properties between the copper redox center and the disulphide bridge bound to the substrate are investigated and briefly discussed.

Azurin↗
PubMed2004

Toward the understanding of the structure and dynamics of protein-carbohydrate interactions: molecular dynamics studies of the complexes between hevein and oligosaccharidic ligands.

Herein we study, through all atom molecular dynamics simulations, the complex between hevein and two N-acetylated chitin oligomers, namely N,N(')-diacetylchitobiose and N,N('),N(")-triacetylchitotriose. The results of the simulations for two disaccharide complexes and one trisaccharide complex show that a carbohydrate oligomer is able to move on the surface of the relatively flat binding pocket of hevein, therefore occupying different binding subpockets. Statistical analysis methods were also applied in order to define the principal overall motions in the complexes, showing how the different ligands in the simulations modulate the protein motions. The oligosaccharide binding can be considered as defined by a subtle balance between enthalpic (formation of intermolecular interactions between the ligand and the receptor) and entropic (due mainly to the possibility for the sugar to move on the surface of the protein domain) effects, determining multiple binding conformations. This structural and dynamical view could parallel the results obtained by regularly used restrained MD simulations based on NOE NMR data that provide a well defined structure for both the disaccharide and trisaccharide complexes, and agrees with the observations for longer oligosaccharide chains.

Antimicrobial Cationic Peptides↗
PubMed2004

Conformational analysis and dynamics of mannobiosides and mannotriosides using Monte Carlo/stochastic dynamics simulations.

The conformation and dynamics of alpha-(1-->2)-mannobioside, alpha-(1-->6)-mannobioside, and of the trisaccharide alpha-Man-(1-->2)-alpha-Man-(1-->6)-alpha- Man-OMe were studied using Monte Carlo/stochastic dynamics (MC/SD) simulations, the AMBER* force field, and the GB/SA implicit water solvation model. The results are in agreement with available experimental data.

Carbohydrate Conformation↗
PubMed2006

Dynamic light scattering in turbid colloidal dispersions: a comparison between the modified flat-cell light-scattering instrument and 3D dynamic light-scattering instrument.

It remains a challenge to measure dynamics in dense colloidal systems. Multiple scattering and low light-transmission rates often hinder measurements in such systems. One of the well-established techniques for overcoming the problem of multiple scattering is cross-correlation techniques such as 3D dynamic light scattering (3D-DLS). However, a high degree of multiple scattering, i.e., vanishing single-scattering contribution in the signal, limits the use of the 3D-DLS technique. We present another approach to measure turbid media by way of upgrading our flat-cell light-scattering instrument (FCLSI). This instrument was originally designed for static light-scattering (SLS) experiments and is similar to a Fraunhofer setup, which features a flat sample cell. The thickness of the flat sample cell can be varied from 13 mum to 5 mm. The small thickness increases the transmission, reduces multiple scattering to a negligible amount, and therefore enables the investigation of dense colloidal systems. We upgraded this instrument for DLS measurements by the installation of an optical single-mode fiber detector in the forward scattering regime. We present our instrumentation and subsequently test its limits using a concentration series of a turbid colloidal suspension. We compare the performances of our modified flat-cell light-scattering instrument with that of standard DLS and with that of 3D-DLS. We show that 3D-DLS and FCLSI only have a comparable performance if the length of the light path in the sample using the 3D-DLS is reduced to a minimum. Otherwise, the FCLSI has some advantage.

Journal Article↗
PubMed2005

Release dynamic process identification for a cement based material in various leaching conditions. Part II. Modelling the release dynamics for different leaching conditions.

This paper deals with process identification and model development for the case of a porous reference material leaching under certain hydrodynamic conditions. Four different dynamic leaching tests have been applied in order to take into account different types of solid/liquid contact conditions corresponding to various real leaching scenarios: monolithic and granular material with sequential eluate renewal, and granular material and continuously renewed eluate with different hydrodynamic conditions (dispersion, residence time). A coupled chemical-mass transfer model has been developed to describe the leaching behaviour under all experimental conditions. Diffusion has been considered as the mass transport mechanism inside the saturated porous material and dispersive convection as that in the leachate. Two specific phenomena have been identified and considered in the model: (i) the early surface dissolution of the material which results in high Ca concentration and (ii) the late weak dissolution of Na and K giving rise to a long-term residual release. The intrinsic material parameters such as the initial concentrations in the pore water and solid phases were determined by applying equilibrium leaching tests and geochemical modelling. Diffusion coefficients for different elements and the late solubility of alkalines have been found to reach the same values in the four tests. The estimated values of the surface dissolution kinetic constant have shown a dependence on leachate hydrodynamics when the thickness of the degraded layer is nearly the same in the four tests (intrinsic parameter of the material). The competition between the four main dynamic processes, i.e. diffusion, convection, late dissolution, and surface dissolution, has been emphasized and compared in the four leaching tests: the hydrodynamic dispersion and the residence time had no effect on the leaching behaviour of alkalines, which is controlled by diffusion, whereas the behaviour of calcium (a major element of the material) was strongly influenced. This has significant effects on eluate pH values and on the concentration of Pb (the monitored pollutant). The model was then applied to simulate a landfill scenario in the case of a stabilized/solidified incinerator residue containing heavy metals and chloride. A high rain infiltration level and the use of small blocs are favourable conditions for enhanced pollutant release.

Construction Materials↗
PubMed2005

When do mixotrophs specialize? Adaptive dynamics theory applied to a dynamic energy budget model.

In evolutionary history, several events have occurred at which mixotrophs specialized into pure autotrophs and heterotrophs. We studied the conditions under which such events take place, using the Dynamic Energy Budget (DEB) theory for physiological rules of the organisms' metabolism and Adaptive Dynamics (AD) theory for evolutionary behavior of parameter values. We modeled a population of mixotrophs that can take up dissolved inorganic nutrients by autotrophic assimilation and detritus by heterotrophic assimilation. The organisms have a certain affinity for both pathways; mutations that occur in the affinities enable the population to evolve. One of the possible evolutionary outcomes is a branching point which provides an opportunity for the mixotrophic population to split up and specialize into separate autotrophs and heterotrophs. Evolutionary branching is not a common feature of the studied system, but is found to occur only under specific conditions. These conditions depend on intrinsic properties such as the cost function, the level of the costs and the boundaries of the trait space: only at intermediate cost levels and when an explicit advantage exists to pure strategies over mixed ones may evolutionary branching occur. Usually, such an advantage (and hence evolutionary branching) can be induced by interference between the two affinities, but this result changes due to the constraints on the affinities. Now, only some of the more complicated cost functions give rise to a branching point. In contrast to the intrinsic properties, extrinsic properties such as the total nutrient content or light intensity were found to have no effect on the evolutionary outcomes at all.

Adaptation, Physiological↗
PubMed2005

Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability.

Gene-specific repeat instability is responsible for >36 human diseases. Active instability varies in a tissue-, developmental stage- and locus-specific manner and occurs in both proliferative and non-proliferative cells. In proliferative cells, DNA replication can contribute to repeat instability either by switching the direction of replication, which changes the repeat sequence that serves as the lagging-strand template (origin switching), or by shifting the location of the origin of replication without altering the replication direction (origin shifting). We propose that changes in the dynamics of replication-fork progression, or architecture, will alter the location of the repeat within the single-stranded lagging-strand template, thereby influencing instability (fork shifting). The fork-shift model, which does not require origin relocation, is influenced by cis-elements and trans-factors associated with driving and maintaining replication forks. The fork-shift model can explain some of the complex behaviours of repeat instability because it is dynamic and responsive to variations in epigenomic and locus activity.

DNA Polymerase III↗
PubMed2000

Conformation and dynamic properties of a saturated hydrocarbon chain confined in a model membrane: a Brownian dynamics simulation.

A Brownian dynamics simulation of a saturated hydrocarbon chain with simple mean-field potentials, namely anchorage, orientation and enclosing, reproducing a biological membrane environment is presented. The simulation was performed for a time equivalent to 1.4 micros thanks to the simplicity of our model. The results are compared with those obtained for a hydrocarbon chain simulated in the absence of the membrane potentials but with confinement. With the appropriate choice of parameters, equilibrium properties, such as deuterium order parameter, chain length, tilt angle and geometry, and dynamic properties, such as dihedral angle transition rate, rotational and translational diffusion, recovered from our simulations, correctly reproduced, are consistent with hydrocarbon-derived molecule experimental results and simulation results obtained from other more complex studies.

Hydrocarbons↗
PubMed2000

Molecular dynamics and (2)H-NMR study of the influence of an amphiphilic peptide on membrane order and dynamics.

A molecular dynamics simulation of a fully hydrated model membrane consisting of 12 molecules of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine, one amphiphilic peptide with the sequence acetyl-Lys-Lys-Gly-Leu(16)-Lys-Lys-Ala-amide, and 593 water molecules was performed for 1.06 ns (Belohorcova, K., J. H. Davis, T. B. Woolf, and B. Roux. 1997. Biophys. J. 73:3039-3055). The analysis presented here is primarily focused on the phospholipid component and the results are compared with experimental (2)H-NMR studies of the lipid component of mixtures of the same peptide and lipid at a molar ratio of 1:32, and with earlier studies of closely related peptide/lipid mixtures. The phospholipid chain and headgroup isomer populations and isomerization rates compare favorably with previous simulations and experimental measurements. Of particular interest is the effect of the peptide on the phospholipid headgroup and hydrocarbon chain orientational order calculated from the simulation, which also agree well with experimental measurements performed on this and closely related systems. Comparison of the experimental results with the simulations not only shows that there is significant agreement between the two methods, but also provides new insight into the effect of the peptide on the lipid dynamics. In particular, these results confirm that a membrane spanning peptide has little effect on lipid chain order, and bilayer thickness if its hydrophobic length closely matches the lipid hydrocarbon thickness. In addition, we find that the peptide can have a strong ordering effect if it is longer than the lipid hydrophobic thickness.

Amino Acid Sequence↗
PubMed2000

Molecular dynamics simulations of protein-tyrosine phosphatase 1B. II. substrate-enzyme interactions and dynamics.

Molecular dynamics simulations of protein tyrosine phosphatase 1B (PTP1B) complexed with the phosphorylated peptide substrate DADEpYL and the free substrate have been conducted to investigate 1) the physical forces involved in substrate-protein interactions, 2) the importance of enzyme and substrate flexibility for binding, 3) the electrostatic properties of the enzyme, and 4) the contribution from solvation. The simulations were performed for 1 ns, using explicit water molecules. The last 700 ps of the trajectories was used for analysis determining enthalpic and entropic contributions to substrate binding. Based on essential dynamics analysis of the PTP1B/DADEpYL trajectory, it is shown that internal motions in the binding pocket occur in a subspace of only a few degrees of freedom. In particular, relatively large flexibilities are observed along several eigenvectors in the segments: Arg(24)-Ser(28), Pro(38)-Arg(47), and Glu(115)-Gly(117). These motions are correlated to the C- and N-terminal motions of the substrate. Relatively small fluctuations are observed in the region of the consensus active site motif (H/V)CX(5)R(S/T) and in the region of the WPD loop, which contains the general acid for catalysis. Analysis of the individual enzyme-substrate interaction energies revealed that mainly electrostatic forces contribute to binding. Indeed, calculation of the electrostatic field of the enzyme reveals that only the field surrounding the binding pocket is positive, while the remaining protein surface is characterized by a predominantly negative electrostatic field. This positive electrostatic field attracts negatively charged substrates and could explain the experimentally observed preference of PTP1B for negatively charged substrates like the DADEpYL peptide.

Amino Acid Sequence↗
PubMed2001

Dynamical properties of a hydrated lipid bilayer from a multinanosecond molecular dynamics simulation.

A fully hydrated dimiristoylphosphatidylcholine (DMPC) bilayer has been studied by a molecular dynamics simulation. The system, which consisted of 64 DMPC molecules and 1792 water molecules, was run in the NVE ensemble at a temperature of 333 K for a total of 10 ns. The resulting trajectory was used to analyze structural and dynamical quantities. The electron density, bilayer spacing, and order parameters (S(CD)), based on the AMBER forcefield and SPCE water model are in good agreement with previous calculations and experimental data. The simulation reveals evidence for two types of lateral diffusive behavior: cage hopping and that of a two-dimensional liquid. The lateral diffusion coefficient is 8 x 10(-8) cm(2)/s. We characterize the rotational motion, and find that the lipid tail rotation (D(rot_tail) = -0.04 rad(2)/ns) is slower then the head group rotation (D(rot_hg) = 2.2 rad(2)/ns), which is slower than the overall in plane (D(rot) = 3.2 rad(2)/ns) for the lipid molecule.

Computer Simulation↗
PubMed2002

Molecular dynamics simulation of the RNA complex of a double-stranded RNA-binding domain reveals dynamic features of the intermolecular interface and its hydration.

The interaction between double-stranded RNA (dsRNA) and the third double-stranded domain (dsRBD) from Drosophila Staufen protein represents a paradigm to understand how the dsRBD protein family, one of the most common RNA-binding protein units, binds dsRNA. The nuclear magnetic resonance (NMR) structure of this complex and the x-ray structure of another family member revealed the stereochemical basis for recognition, but also raised new questions. Although the crystallographic studies revealed a highly ordered interface containing numerous water-mediated contacts, NMR suggested extensive residual motion at the interface. To address how interfacial motion contributes to molecular recognition in the dsRBD-dsRNA system, we conducted a 2-ns molecular dynamics simulation of the complex derived from Staufen protein and of the separate protein and RNA components. The results support the observation that a high degree of conformational flexibility is retained upon complex formation and that this involves interfacial residues that are critical for dsRBD-dsRNA binding. The structural origin of this residual flexibility is revealed by the analysis of the trajectory of motion. Individual basic side chains switch continuously from one RNA polar group to another with a residence time seldom exceeding 100 ps, while retaining favorable interaction with RNA throughout much of the simulation. Short-lived water molecules mediate some of these interactions for a large fraction of the trajectory studied here. This result indicates that water molecules are not statically associated with the interface, but continuously exchange with the bulk solvent on a 1-10-ps time scale. This work provides new insight into dsRBD-dsRNA recognition and builds upon a growing body of evidence, suggesting that short-lived dynamic interactions play important roles in protein-nucleic acid interactions.

Binding Sites↗
PubMed2003

Protein dynamics, thermal stability, and free-energy landscapes: a molecular dynamics investigation.

Proteins have a complex free-energy landscape because of their rich topology and the nature of their nonbonded interaction potential. This has important consequences because the roughness of the landscape affects the ease with which a chain folds and also determines the dynamic behavior of the folded structure, thus influencing its functional and stability properties. A detailed description of the free-energy landscape is therefore of paramount importance for a quantitative understanding of the relationships between structure, dynamics, stability, and functional behavior of proteins. The free-energy landscape of a protein is a high-dimensional hypersurface, difficult to rationalize. Therefore, achieving its detailed graphical representation in a way that goes beyond the familiar funnel-like free-energy model is still a big challenge. We describe here an approach based on global structural parameters that allows a two-dimensional representation of the free-energy landscape from simulated atomic trajectories. As shown in this and in the accompanying article, our representation of the landscape, combined with other conformational analyses, provides valuable information on its roughness and on how atomic trajectories evolve with time.

Algorithms↗
PubMed2004

Temperature-dependent conformational transitions and hydrogen-bond dynamics of the elastin-like octapeptide GVG(VPGVG): a molecular-dynamics study.

A joint experimental/theoretical investigation of the elastin-like octapeptide GVG(VPGVG) was carried out. In this article a comprehensive molecular-dynamics study of the temperature-dependent folding and unfolding of the octapeptide is presented. The current study, as well as its experimental counterpart (see companion article in this issue) find that this peptide undergoes an inverse temperature transition (ITT), leading to a folding at approximately 40-60 degrees C. In addition, an unfolding transition is identified at unusually high temperatures approaching the normal boiling point of water. Due to the small size of the system, two broad temperature regimes are found: the ITT regime at approximately 10-60 degrees C and the unfolding regime at approximately T > 60 degrees C, where the peptide has a maximum probability of being folded at T approximately 60 degrees C. A detailed molecular picture involving a thermodynamic order parameter, or reaction coordinate, for this process is presented along with a time-correlation function analysis of the hydrogen-bond dynamics within the peptide as well as between the peptide and solvating water molecules. Correlation with experimental evidence and ramifications on the properties of elastin are discussed.

Biomimetic Materials↗
PubMed2004

Dynamic water networks in cytochrome C oxidase from Paracoccus denitrificans investigated by molecular dynamics simulations.

We present a molecular dynamics study of cytochrome c oxidase from Paracoccus denitrificans in the fully oxidized state, embedded in a fully hydrated dimyristoylphosphatidylcholine lipid bilayer membrane. Parallel simulations with different levels of protein hydration, 1.125 ns each in length, were carried out under conditions of constant temperature and pressure using three-dimensional periodic boundary conditions and full electrostatics to investigate the distribution and dynamics of water molecules and their corresponding hydrogen-bonded networks inside cytochrome c oxidase. The majority of the water molecules had residence times shorter than 100 ps, but a few water molecules are fixed inside the protein for up to 1.125 ns. The hydrogen-bonded network in cytochrome c oxidase is not uniformly distributed, and the degree of water arrangement is variable. The average number of solvent sites in the proton-conducting K- and D-pathways was determined. In contrast to single water files in narrow geometries we observe significant diffusion of individual water molecules along these pathways. The highly fluctuating hydrogen-bonded networks, combined with the significant diffusion of individual water molecules, provide a basis for the transfer of protons in cytochrome c oxidase, therefore leading to a better understanding of the mechanism of proton pumping.

Computer Simulation↗
PubMed1995

Solvent effect on phosphatidylcholine headgroup dynamics as revealed by the energetics and dynamics of two gel-state bilayer headgroup structures at subzero temperatures.

The packing and dynamics of lipid bilayers at the phosphocholine headgroup region within the temperature range of -40 to -110 degrees C have been investigated by solid-state nuclear magnetic resonance (NMR) measurements of selectively deuterium-labeled H2O/dimyristoylphosphatidylcholine (DMPC) bilayers. Two coexisting signals with 2H NMR quadrupolar, splittings of 36.1 and 9.3 (or smaller) kHz were detected from the -CD3 of choline methyl group. These two signals have been assigned to two coexisting gel-state headgroup structures with fast rotational motion of -CD3 and -N(CD3)3 group, respectively, with a threefold symmetry. The largest quadrupolar splitting of the NMR signal detected from the -CD2 of C alpha and C beta methylene segment was found to be 115.2 kHz, which is 10% lower than its static value of 128.2 kHz. Thus, there are extensive motions of the entire choline group of gel-state phosphatidylcholine bilayers even at a subzero temperature of -110 degrees C. These results strongly support the previous suggestion (E. J. Dufourc, C. Mayer, J. Stohrer, G. Althoff, and G. Kothe, 1992, Biophys. J. 61:42-57) that 31P chemical shift tensor elements of DMPC determined under similar conditions are not the rigid static values. The free energy difference between the two gel-state headgroup structures was determined to be 26.3 +/- 0.9 kJ/mol for fully hydrated bilayers. Furthermore, two structures with similar free energy difference were also detected for "frozen" phosphorylcholine chloride solution in a control experiment, leading to the conclusion that the two structures may be governed solely by the energetics of fully hydrated phosphocholine headgroup. The intermolecular interactions among lipids, however, stabilize the static headgroup structure as evidenced by the apparently lower free energy difference between the two structures for partially hydrated lipid bilayers. Evidence is also presented to suggest that one of the headgroup structures with trimethylammonium group rotation, which is not compatible with the static headgroup structure in crystals, is due to the dielectric relaxation of the slowly reorienting inter bilayer water molecules near the physical edge of membrane surface. Finally, a molecular model of the hydration-induced conformational changes at the torsion angle a5 of the O-C-CN+ bond is proposed to explain the two detected coexisting headgroup structures. These results emphasize the important role of the trimethylammonium group in monitoring the structure and dynamics of the lipid headgroup.

Deuterium↗
PubMed1997

Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics.

Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.

Amino Acid Sequence↗
PubMed1997

Salt effects on the structure and internal dynamics of superhelical DNAs studied by light scattering and Brownian dynamics.

Using laser light scattering, we have measured the static and dynamic structure factor of two different superhelical DNAs, p1868 (1868 bp) and simian virus 40 (SV40) (5243 bp), in dilute aqueous solution at salt concentrations between 1 mM and 3 M NaCl. For both DNA molecules, Brownian dynamics (BD) simulations were also performed, using a previously described model. A Fourier mode decomposition procedure was used to compute theoretical light scattering autocorrelation functions (ACFs) from the BD trajectories. Both measured and computed autocorrelation functions were then subjected to the same multiexponential decomposition procedure. Simulated and measured relaxation times as a function of scattering angle were in very good agreement. Similarly, computed and measured static structure factors and radii of gyration agreed within experimental error. One main result of this study is that the amplitudes of the fast-relaxing component in the ACF show a peak at 1 M salt concentration. This nonmonotonic behavior might be caused by an initial increase in the amplitudes of internal motions due to diminishing long-range electrostatic repulsions, followed by a decrease at higher salt concentration due to a compaction of the structure.

Biophysical Phenomena↗