Local Molecular Field Theory for Nonequilibrium Systems.

We provide a framework for extending equilibrium local molecular field (LMF) theory to a statistical ensemble evolving under a time-dependent applied field. In this context, the self-consistency of the original LMF equation is achieved dynamically, which provides an efficient method for computing the equilibrium LMF potential, in addition to providing the nonequilibrium generalization. As a concrete example, we investigate water confined between hydrophobic or charged walls, systems that are very sensitive to the treatment of long-ranged electrostatics.

Adaptations for Pressure and Temperature Effects on Loop Motion in and Dihydrofolate Reductase.

Determining how enzymes in piezophilic microbes function at high pressure can give insights into how life adapts to living at high pressure. Here, the effects of pressure and temperature on loop motions are compared (Ec) and (Mp) dihydrofolate reductase (DHFR) via molecular dynamics simulations at combinations of the growth temperature and pressure of the two organisms. Analysis indicates that a flexible CD loop in MpDHFR is an adaptation for cold because it makes the adenosine binding subdomain more flexible.

Effects of Pressure and Temperature on the Atomic Fluctuations of Dihydrofolate Reductase from a Psychropiezophile and a Mesophile.

Determining the effects of extreme conditions on proteins from "extremophilic" and mesophilic microbes is important for understanding how life adapts to living at extremes as well as how extreme conditions can be used for sterilization and food preservation. Previous molecular dynamics simulations of dihydrofolate reductase (DHFR) from a psychropiezophile (cold- and pressure-loving), (Mp), and a mesophile, (Ec), at various pressures and temperatures indicate that atomic fluctuations, which are important for enzyme function, increase with both temperature and pressure. Here, the factors that cause increases in atomic fluctuations in the simulations are examined.

Quasiharmonic Analysis of the Energy Landscapes of Dihydrofolate Reductase from Piezophiles and Mesophiles.

A quasiharmonic analysis (QHA) method is used to compare the potential energy landscapes of dihydrofolate reductase (DHFR) from a piezophile (pressure-loving organism), Moritella profunda (Mp), and a mesophile, Escherichia coli (Ec). The QHA method considers atomic fluctuations of the protein as motions of an atom in a local effective potential created by neighboring atoms and quantitates it in terms of effective force constants, isothermal compressibilities, and thermal expansivities. The analysis indicates that the underlying potential energy surface of MpDHFR is inherently softer than that of EcDHFR.

Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations.

Positional fluctuations of an atom in a protein can be described as motion in an effective local energy minimum created by the surrounding protein atoms. The dependence of atomic fluctuations on both temperature (T) and pressure (P) has been used to probe the nature of these minima, which are generally described as harmonic in experiments such as x-ray crystallography and neutron scattering. Here, a quasiharmonic analysis method is presented in which the P-T dependence of atomic fluctuations is in terms of an intrinsic isobaric thermal expansivity α and an intrinsic isothermal compressibility κ.

Extreme biophysics: Enzymes under pressure.

A critical question about piezophilic (pressure-loving) microbes is how their constituent molecules maintain function under high pressure. Here, factors are examined that may lead to the increased activity under pressure in dihydrofolate reductase from the piezophilic Moritella profunda compared to the homologous enzyme from the mesophilic Escherichia coli. Molecular dynamics simulations are performed at various temperatures and pressures to examine how pressure affects the flexibility of the enzymes from these two microbes, since both stability and flexibility are necessary for enzyme activity.

On the Equivalence of Schemes for Simulating Bilayers at Constant Surface Tension.

Lipid bilayers are simulated using flexible simulation cells in order to allow for relaxations in area per lipid as bilayer content and temperature are varied. We develop a suite of Monte Carlo (MC) moves designed to generate constant surface tension γ and constant pressure P and find that the NPT partition function proposed by Attard [J. Chem.

Understanding the phase behavior of coarse-grained model lipid bilayers through computational calorimetry.

We study the phase behavior of saturated lipids as a function of temperature and tail length for two coarse-grained models: the soft-repulsive model typically employed with dissipative particle dynamics (DPD) and the MARTINI model. We characterize the simulated transitions through changes in structural properties, and we introduce a computational method to monitor changes in enthalpy, as is done experimentally with differential scanning calorimetry. The lipid system experimentally presents four different bilayer phases - subgel, gel, ripple, and fluid - and the DPD model describes all of these phases structurally while MARTINI describes a single order-disorder transition between the gel and the fluid phases.

Molecular Monte Carlo Simulations Using Graphics Processing Units: To Waste Recycle or Not?

In the waste recycling Monte Carlo (WRMC) algorithm, (1) multiple trial states may be simultaneously generated and utilized during Monte Carlo moves to improve the statistical accuracy of the simulations, suggesting that such an algorithm may be well posed for implementation in parallel on graphics processing units (GPUs). In this paper, we implement two waste recycling Monte Carlo algorithms in CUDA (Compute Unified Device Architecture) using uniformly distributed random trial states and trial states based on displacement random-walk steps, and we test the methods on a methane-zeolite MFI framework system to evaluate their utility. We discuss the specific implementation details of the waste recycling GPU algorithm and compare the methods to other parallel algorithms optimized for the framework system.

Waste-recycling Monte Carlo with optimal estimates: application to free energy calculations in alloys.

The estimator proposed recently by Delmas and Jourdain for waste-recycling Monte Carlo achieves variance reduction optimally with respect to a control variate that is evaluated directly using the simulation data. Here, the performance of this estimator is assessed numerically for free energy calculations in generic binary alloys and is compared to those of other estimators taken from the literature. A systematic investigation with varying simulation parameters of a simplified system, the anti-ferromagnetic Ising model, is first carried out in the transmutation ensemble using path-sampling.

Molecular simulation of the effect of cholesterol on lipid-mediated protein-protein interactions.

Experiments and molecular simulations have shown that the hydrophobic mismatch between proteins and membranes contributes significantly to lipid-mediated protein-protein interactions. In this article, we discuss the effect of cholesterol on lipid-mediated protein-protein interactions as function of hydrophobic mismatch, protein diameter and protein cluster size, lipid tail length, and temperature. To do so, we study a mesoscopic model of a hydrated bilayer containing lipids and cholesterol in which proteins are embedded, with a hybrid dissipative particle dynamics-Monte Carlo method.

Molecular simulation of the DMPC-cholesterol phase diagram.

In this paper, we present a coarse-grained model of a hydrated saturated phospholipid bilayer (dimyristoylphosphatidylcholine, DMPC) containing cholesterol that we study using a hybrid dissipative particle dynamics-Monte Carlo method. This approach allows us to reach the time and length scales necessary to study structural and mechanical properties of the bilayer at various temperatures and cholesterol concentrations. The properties studied are the area per lipid, condensation, bilayer thickness, tail order parameters, bending modulus, and area compressibility.

Alcohol solubility in a lipid bilayer: Efficient grand-canonical simulation of an interfacially active molecule.

We derive a new density-biased Monte Carlo technique which preserves detailed balance and improves the convergence of grand-canonical simulations of a species with a strong preference for an interfacial region as compared to the bulk. This density-biasing technique is applied to the solubility of "alcohol" molecules in a mesoscopic model of the lipid bilayer, a system which has anesthetic implications but is poorly understood.

Accurate thermodynamics for short-ranged truncations of Coulomb interactions in site-site molecular models.

Coulomb interactions are present in a wide variety of all-atom force fields. Spherical truncations of these interactions permit fast simulations but are problematic due to their incorrect thermodynamics. Herein we demonstrate that simple analytical corrections for the thermodynamics of uniform truncated systems are possible.

Interplay of local hydrogen-bonding and long-ranged dipolar forces in simulations of confined water.

Spherical truncations of Coulomb interactions in standard models for water permit efficient molecular simulations and can give remarkably accurate results for the structure of the uniform liquid. However, truncations are known to produce significant errors in nonuniform systems, particularly for electrostatic properties. Local molecular field (LMF) theory corrects such truncations by use of an effective or restructured electrostatic potential that accounts for effects of the remaining long-ranged interactions through a density-weighted mean field average and satisfies a modified Poisson's equation defined with a Gaussian-smoothed charge density.

Attraction between like-charged walls: Short-ranged simulations using local molecular field theory.

Effective attraction between like-charged walls mediated by counterions is studied using local molecular field (LMF) theory. Monte Carlo simulations of the "mimic system" given by LMF theory, with short-ranged "Coulomb core" interactions in an effective single particle potential incorporating a mean-field average of the long-ranged Coulomb interactions, provide a direct test of the theory, and are in excellent agreement with more complex simulations of the full Coulomb system by Moreira and Netz [Eur. Phys.