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Biomedical subjects

B J Berne

Publications and source records attributed to B J Berne.

At least 19 recordsLinked to original sources
PubMed2006

Aggregation and dispersion of small hydrophobic particles in aqueous electrolyte solutions.

The effect of salts on the solvent-induced interactions between hydrophobic particles dispersed in explicit aqueous solution is investigated as a function of the salt's ionic charge density by molecular dynamics simulations. We demonstrate that aggregates of the hydrophobic particles can be formed or dissolved in response to changes in the charge density of the ions. Ions with high charge density increase the propensity of the hydrophobic particles to aggregate. This corresponds to stronger hydrophobic interactions and a decrease in the solubility (salting-out) of the hydrophobic particles. Ions with low charge density can either increase or decrease the propensity for aggregation depending on whether the concentration of the salt is low or high, respectively. At low concentrations of low charge density ions, the aggregate forms a "micelle-like" structure in which the ions are preferentially adsorbed at the surface of the aggregate. These "micelle-like" structures can be soluble in water so that the electrolyte can both increase the solubility and increase aggregation at the same time. We also find, that at the concentration of the hydrophobic particles studied (approximately 0.75 m), the aggregation process resembles a first-order transition in finite systems.

Absorption↗
PubMed2006

Hydrophobic aided replica exchange: an efficient algorithm for protein folding in explicit solvent.

A hydrophobic aided replica exchange method (HAREM) is introduced to accelerate the simulation of all-atom protein folding in explicit solvent. This method is based on exaggerating the hydrophobic effect of various protein amino acids in water by attenuating the protein-water attractive interactions (mimicking the Chaperon effect) while leaving other interactions among protein atoms and water molecules unchanged. The method is applied to a small representative protein, the alpha-helix 3K(I), and it is found that the HAREM method successfully folds the protein within 4 ns, while the regular replica exchange method does not fold the same protein within 5 ns, even with many more replicas.

Algorithms↗
PubMed2006

Elastic bag model for molecular dynamics simulations of solvated systems: application to liquid water and solvated peptides.

The fluctuating elastic boundary (FEB) model for molecular dynamics has recently been developed and validated through simulations of liquid argon. In the FEB model, a flexible boundary which consists of particles connected by springs is used to confine the solvated system, thereby eliminating the need for periodic boundary conditions. In this study, we extend this model to the simulation of bulk water and solvated alanine dipeptide. Both the confining potential and boundary particle interaction functions are modified to preserve the structural integrity of the boundary and prevent the leakage of the solute-solvent system through the boundary. A broad spectrum of structural and dynamic properties of liquid water are computed and compared with those obtained from conventional periodic boundary condition simulations. The applicability of the model to biomolecular simulations is investigated through the analysis of conformational population distribution of solvated alanine dipeptide. In most cases we find remarkable agreement between the two simulation approaches.

Hydrogen Bonding↗
PubMed2006

Dynamics of water confined in the interdomain region of a multidomain protein.

Molecular dynamics simulations are performed to study the dynamics of interfacial water confined in the interdomain region of a two-domain protein, BphC enzyme. The results show that near the protein surface the water diffusion constant is much smaller and the water-water hydrogen bond lifetime is much longer than that in bulk. The diffusion constant and hydrogen bond lifetime can vary by a factor of as much as 2 in going from the region near the hydrophobic domain surface to the bulk. Water molecules in the first solvation shell persist for a much longer time near local concave sites than near convex sites. Also, the water layer survival correlation time shows that on average water molecules near the extended hydrophilic surfaces have longer residence times than those near hydrophobic surfaces. These results indicate that local surface curvature and hydrophobicity have a significant influence on water dynamics.

Computer Simulation↗
PubMed2005

Transport properties of normal liquid helium: comparison of various methodologies.

We revisit the problem of self-diffusion in normal liquid helium above the lambda transition. Several different methods are applied to compute the velocity autocorrelation function. Since it is still impossible to determine the exact result for the velocity autocorrelation function from simulation, we appeal to the computation of short-time moments to determine the accuracy of the different approaches at short times. The main conclusion reached from our study is that both the quantum mode-coupling theory and the numerical analytic continuation approach must be regarded as a viable and competitive methods for the computation of dynamical properties of quantum systems.

Journal Article↗
PubMed2005

Replica exchange with solute tempering: a method for sampling biological systems in explicit water.

An innovative replica exchange (parallel tempering) method called replica exchange with solute tempering (REST) for the efficient sampling of aqueous protein solutions is presented here. The method bypasses the poor scaling with system size of standard replica exchange and thus reduces the number of replicas (parallel processes) that must be used. This reduction is accomplished by deforming the Hamiltonian function for each replica in such a way that the acceptance probability for the exchange of replica configurations does not depend on the number of explicit water molecules in the system. For proof of concept, REST is compared with standard replica exchange for an alanine dipeptide molecule in water. The comparisons confirm that REST greatly reduces the number of CPUs required by regular replica exchange and increases the sampling efficiency. This method reduces the CPU time required for calculating thermodynamic averages and for the ab initio folding of proteins in explicit water.

Algorithms↗
PubMed2005

Structure and dynamics of the solvation of bovine pancreatic trypsin inhibitor in explicit water: a comparative study of the effects of solvent and protein polarizability.

To isolate the effects of the inclusion of polarizability in the force field model on the structure and dynamics of the solvating water in differing electrostatic environments of proteins, we present the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in water with force fields that explicitly include polarization for both the protein and the water. We use three model potentials for water and two model potentials for the protein. Two of the water models and one of the protein models are polarizable. A total of six systems were simulated representing all combinations of these polarizable and nonpolarizable protein and water force fields. We find that all six systems behave in a similar manner in regions of the protein that are weakly electrostatic (either hydrophobic or weakly hydrophilic). However, in the vicinity of regions of the protein with relatively strong electrostatic fields (near positively or negatively charged residues), we observe that the water structure and dynamics are dependent on both the model of the protein and the model of the water. We find that a large part of the dynamical dependence can be described by small changes in the local environments of each region that limit the local density of non-hydrogen-bonded waters, precisely the water molecules that facilitate the dynamical relaxation of the water-water hydrogen bonds. We introduce a simple method for rescaling for this effect. When this is done, we are able to effectively isolate the influence of polarizability on the dynamics. We find that the solvating water's relaxation is most affected when both the protein and the water models are polarizable. However, when only one model (or neither) is polarizable, the relaxation is similar regardless of the models used.

Animals↗
PubMed2005

Observation of a dewetting transition in the collapse of the melittin tetramer.

Marked hydration changes occur during the self-assembly of the melittin protein tetramer in water. Hydrophobicity induces a drying transition in the gap between simple sufficiently large (more than 1 nm(2)) strongly hydrophobic surfaces as they approach each other, resulting in the subsequent collapse of the system, as well as a depletion of water next to single surfaces. Here we investigate whether the hydrophobic induced collapse of multidomain proteins or the formation of protein oligimers exhibits a similar drying transition. We performed computer simulations to study the collapse of the tetramer of melittin in water, and observed a marked water drying transition inside a nanoscale channel of the tetramer (with a channel size of up to two or three water-molecule diameters). This transition, although occurring on a microscopic length scale, is analogous to a first-order phase transition from liquid to vapour. We find that this drying is very sensitive to single mutations of the three isoleucines to less hydrophobic residues and that such mutations in the right locations can switch the channel from being dry to being wet. Thus, quite subtle changes in hydrophobic surface topology can profoundly influence the drying transition. We show that, even in the presence of the polar protein backbone, sufficiently hydrophobic protein surfaces can induce a liquid-vapour transition providing an enormous driving force towards further collapse. This behaviour was unexpected because of the absence of drying in the collapse of the multidomain protein 2,3-dihydroxybiphenyl dioxygenase (BphC).

Dioxygenases↗
PubMed2005

Polarizable molecules in the vibrational spectroscopy of water.

We examine the role of electronic polarizability in water on short (tens of femtoseconds), intermediate (hundreds of femtoseconds), and long (approximately 1 ps) time scales by comparing molecular dynamics results to experimental data for vibrational spectroscopy of HOD in liquid D2O. Because the OH absorption frequency is sensitive to the details of the atomic forces experienced in the liquid, our results provide important quantitative comparisons for several popular empirical water potentials. When compared with their fixed-charge counterparts, the polarizable models give similar slower long time constants for the decay of vibrational correlations and re-orientational motion that is in better agreement with experiments. Polarizable potentials yield qualitatively dissimilar predictions for frequency fluctuations and transition dipole moment fluctuations at equilibrium. Models that confine the polarizability to the plane of the molecule (i.e., TIP4P-FQ) overestimate the width of the distribution describing frequency fluctuations by more than a factor of two. These models also underestimate the amplitude of the hydrogen-bond stretch at 170 cm(-1). A potential that has both an out-of-plane polarization and fluctuating charges, POL5-TZ, compares best with experiments. We interpret our findings in terms of microscopic dynamics and make suggestions that may improve the quality of emerging polarizable force fields for water.

Journal Article↗
PubMed2005

Hydrogen-bond dynamics in the air-water interface.

Hydrogen-bond (H-bond) dynamics in the air-water interface is studied by molecular dynamics simulations. The analysis reveals that the dynamics of breaking and forming hydrogen bonds in the air-water interface is faster than that in bulk water for the polarizable water models. This is in contrast to the results found on a protein surface. We show that the difference stems from more rapid translational diffusion in the interface. When the effect of pair diffusion is eliminated, the hydrogen-bond dynamics in the interface is observed to be slower than that in the bulk. This occurs because the number of water molecules adjacent to a hydrogen-bonded pair and available to accept or donate a hydrogen bond is smaller in the interface than in the bulk. The comparison between polarizable water models and fixed-charge models highlights the potential importance of the polarization effect in the water-vapor interface.

Air↗
PubMed2005

Elastic bag model for molecular dynamics simulations of solvated systems: application to liquid argon.

A new approach is developed to study the dynamics of the localized process in solutions and other condensed phase systems. The approach employs a fluctuating elastic boundary (FEB) model which encloses the simulated system in an elastic bag that mimics the effects of the bulk solvent. This alleviates the need for periodic boundary conditions and allows for a reduction in the number of solvent molecules that need to be included in the simulation. The boundary bag is modeled as a mesh of quasi-particles connected by elastic bonds. The FEB model allows for volume and density fluctuations characteristic of the bulk system, and the shape of the boundary fluctuates during the course of the simulation to adapt to the configuration fluctuations of the explicit solute-solvent system inside. The method is applied to the simulation of a Lennard-Jones model of liquid argon. Various structural and dynamical quantities are computed and compared with those obtained from conventional periodic boundary simulations. The agreement between the two is excellent in most cases, thus validating the viability of the FEB method.

Argon↗
PubMed2004

Multiple "time step" Monte Carlo simulations: application to charged systems with Ewald summation.

Recently, we have proposed an efficient scheme for Monte Carlo simulations, the multiple "time step" Monte Carlo (MTS-MC) [J. Chem. Phys. 117, 8203 (2002)] based on the separation of the potential interactions into two additive parts. In this paper, the structural and thermodynamic properties of the simple point charge water model combined with the Ewald sum are compared for the MTS-MC real-/reciprocal-space split of the Ewald summation and the common Metropolis Monte Carlo method. We report a number of observables as a function of CPU time calculated using MC and MTS-MC. The correlation functions indicate that speedups on the order of 4.5-7.5 can be obtained for systems of 108-500 waters for n=10 splitting parameter.

Algorithms↗
PubMed2003

Dewetting-induced collapse of hydrophobic particles.

A molecular dynamics study of the depletion of water (drying) around a single and between two hydrophobic nanoscale oblate plates in explicit water as a function of the distance of separation between them, their size, and the strength of the attraction between the plates and the water molecules is presented. A simple macroscopic thermodynamic model based on Young's law successfully predicts drying between the stacked plates and accounts for the free-energy barriers to this drying. However, because drying around a single plate is not macroscopic, a molecular theory is required to describe it. The data are consistent with the rate-determining step in the hydrophobic collapse of the two plates being a large-scale drying fluctuation, characterized by a free-energy barrier that grows with particle size.

Journal Article↗
PubMed2002

Development of a polarizable force field for proteins via ab initio quantum chemistry: first generation model and gas phase tests.

We present results of developing a methodology suitable for producing molecular mechanics force fields with explicit treatment of electrostatic polarization for proteins and other molecular system of biological interest. The technique allows simulation of realistic-size systems. Employing high-level ab initio data as a target for fitting allows us to avoid the problem of the lack of detailed experimental data. Using the fast and reliable quantum mechanical methods supplies robust fitting data for the resulting parameter sets. As a result, gas-phase many-body effects for dipeptides are captured within the average RMSD of 0.22 kcal/mol from their ab initio values, and conformational energies for the di- and tetrapeptides are reproduced within the average RMSD of 0.43 kcal/mol from their quantum mechanical counterparts. The latter is achieved in part because of application of a novel torsional fitting technique recently developed in our group, which has already been used to greatly improve accuracy of the peptide conformational equilibrium prediction with the OPLS-AA force field.1 Finally, we have employed the newly developed first-generation model in computing gas-phase conformations of real proteins, as well as in molecular dynamics studies of the systems. The results show that, although the overall accuracy is no better than what can be achieved with a fixed-charges model, the methodology produces robust results, permits reasonably low computational cost, and avoids other computational problems typical for polarizable force fields. It can be considered as a solid basis for building a more accurate and complete second-generation model.

Algorithms↗
PubMed2001

The free energy landscape for beta hairpin folding in explicit water.

The folding free energy landscape of the C-terminal beta hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and OPLSAA force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME/RESPA. The simulation results show that the hydrophobic core and the beta strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The beta hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.

Amino Acid Sequence↗
PubMed2000

Catalytic tempering: A method for sampling rough energy landscapes by Monte Carlo.

A new Monte Carlo algorithm is presented for the efficient sampling of the Boltzmann distribution of configurations of systems with rough energy landscapes. The method is based on the introduction of a fictitious coordinate y so that the dimensionality of the system is increased by one. This augmented system has a potential surface and a temperature that is made to depend on the new coordinate y in such a way that for a small strip of the y space, called the "normal region," the temperature is set equal to the temperature desired and the potential is the original rough energy potential. To enhance barrier crossing outside the "normal region," the energy barriers are reduced by truncation (with preservation of the potential minima) and the temperature is made to increase with ||y ||. The method, called catalytic tempering or CAT, is found to greatly improve the rate of convergence of Monte Carlo sampling in model systems and to eliminate the quasi-ergodic behavior often found in the sampling of rough energy landscapes.

Journal Article↗
PubMed1997

Novel methods of sampling phase space in the simulation of biological systems.

New advances in molecular dynamics and Monte Carlo simulations have led to impressive increases in the speed of sampling phase space for complex biological systems. These methods have been combined with new fast algorithms for computing long range electrostatic interactions for new polarizable force fields. In addition, new methods for sampling low energy molecular conformations allow the rapid determination of thermodynamically dominant regions on the potential-energy surface. Accurate measures of the rate of phase-space sampling should allow both the optimization and the comparison of methods for a particular problem of interest.

Algorithms↗