Electroosmotic Flow in Nanoscale Parallel-plate Channels: Molecular Simulation Study and Comparison with Classical Poisson–Boltzmann Theory

Molecular dynamics simulations have been carried out for simple electrolyte systems to study the electrokinetically driven osmotic flow in parallel-plate channels of widths ～10–120?nm. The results are compared with the classical theory predictions based on the solution to the Poisson–Boltzmann equation. We find that despite some of the limitations in the Poisson–Boltzmann equation, such as assumption of the Boltzmann distribution for the ions, the classical theory captures the general trend of the variations of the osmotic flow with channel width, as characterized by the mobility of the fluid in channels between ～10 and 120?nm at moderate to low ion concentration. At moderate concentration (corresponding to relatively low surface potential), the classical theory is almost quantitative. The theory and simulation show more disagreement at low concentration, primarily caused by the high surface potential where the assumption of Boltzmann distribution becomes inaccurate. We discuss the limitations of the Poisson–Boltzmann equation as applied to the nanoscale channels.     

Lipid Membrane Structure and Dynamics Studied by All-Atom Molecular Dynamics Simulations of Hydrated Phospholipid Bilayers

Abstract

The structure and dynamics of phosphatidylcholine bilayers are examined by reviewing the results of several nanoseconds of molecular dynamics simulations on a number of bilayer and monolayer models. The lengths of these simulations, the longest single one of which was 2 nanoseconds, were sufficiently long to effectively sample many of the longer-scale motions governing the behaviour of biomembranes. These simulations reproduce many experimental observables well and provide a degree of resolution currently unavailable experimentally.     

Controllers for imposing continuum-to-molecular boundary conditions in arbitrary fluid flow geometries

We present a new parallelised controller for steering an arbitrary geometric region of a molecular dynamics (MD) simulation towards a desired thermodynamic and hydrodynamic state. We show that the controllers may be applied anywhere in the domain to set accurately an initial MD state, or solely at boundary regions to prescribe non-periodic boundary conditions (PBCs) in MD simulations. The mean molecular structure and velocity autocorrelation function remain unchanged (when sampled a few molecular diameters away from the constrained region) when compared with those distributions measured using PBCs. To demonstrate the capability of our new controllers, we apply them as non-PBCs in parallel to a complex MD mixing nano-channel and in a hybrid MD continuum simulation with a complex coupling region. The controller methodology is easily extendable to polyatomic MD fluids.     

Molecular dynamics simulations of submonolayer hexane and pentane films on graphite

We present results of molecular dynamics computer simulations of hexane (C₆H₁₄ or C6) and pentane (C₅H₁₂ or C5) adlayers physisorbed onto a graphite substrate, for various submonolayer coverages. The hexane and pentane molecules incorporate explicit hydrogens and the graphite is modelled as a six-layer all-atom structure. Even though C6 and C5 have different structures at monolayer completion, both systems generally behave similarly in the submonolayer regime and results are in reasonable agreement with experiment for both systems. Specifically, there are four distinct topological regimes involving empty space: at densities closest to full coverage, there are large domains with individual vacancies, then with decreasing density, large vacancy patches appear first, followed by the formation of connected networks of smaller domains with multiple orientations that ultimately separate into individual patches. The energetics and melting behaviour of all systems are readily understood within the framework of the topology presented at various densities.     

Study of the stability of aluminium trimeric clusters in aqueous solutions

Ab initio molecular dynamics (AIMD) based on density functional theory has been used to study small aluminium–oxygen complexes in water. Such Al–O clusters have been seen in several recent mass spectrometry studies. In this study, we have focused on trimeric Al–O clusters. The initial very compact trimeric Al–O structures opened up and formed linear Al–O chains. The typical Al–O coordination number in these chain structures was 5. We have performed long (up to 200 ps) AIMD simulations and these chain structures are stable on the nanosecond time scale. We have also studied the reactivity of the Al–O dimer and solvated Al. We found a formation path for the trimeric cluster, which has a action barrier (0.04 eV) and a reaction free energy of ? 0.55 eV. This suggests that the association of a dimer and a monomer Al–O species is fast and thermodynamically a very favourable process.     

The Glassy Wall Boundary for Simulations of Inhomogeneous Systems

Abstract

For simulations on systems that invlove a physical inhomogeneity at infinite dilution, the usual periodic boundary conditions are inappropriate. In previous studies on such systems, surfaces have been re-introduced in order to contain the particles of the sample. When smooth surfaces are used to contain liquids, undesirable structural artifacts in the liquid are promoted by these surfaces. In this study a rigid but structurally liquid-like containing surface, that we call a glassy wall boundary, is introduced, in an attempt to solve this problem. It serves as a containing surface, but “looks” nearly liquid-like to molecules in the mobile liquid near it. We illustrate the properties of this boundary for a system that consists of an isolated polyion surrounded by SPC water at 300K and ～ 1 gcm^?3. We show that this boundary reduces or eliminates some of the problems caused by a smooth surface.     

A Robust Water Potential Parameterisation

Abstract

We compare molecular dynamics simulation results for the properties of liquid water predicted by four novel water potential models. These models are designed as a combination of parameters taken from the dedicated but brittle TIP3P water potential, and the more flexible but less accurate parameterisations such as the Dreiding and Universal force fields. We find that a hybrid of Dreiding and TIP3P delivers the best results, yielding a density, diffusion coefficient and radial distribution function in good agreement with experiment, performing in some respects even better than the dedicated reference TIP3P model. Another Dreiding based force field predicts semi-quantitative results for the water structure and dynamics while the Universal force field based models are incapable of simulating a condensed phase of water at all, continuing to expand indefinitely. These observations are useful for selecting and designing robust water force field parameterisations that can be used for general simulation purposes.     

Inhibitor binding studies of Mycobacterium tuberculosis MraY (Rv2156c): Insights from molecular modeling,docking, and simulation studies

Abstract

Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (M.tb) or tubercule bacillus, and H37Rv is the most studied clinical strain. The recent development of resistance to existing drugs is a global health-care challenge to control and cure TB. Hence, there is a critical need to discover new drug targets in M.tb. The members of peptidoglycan biosynthesis pathway are attractive target proteins for antibacterial drug development. We have performed in silico analysis of M.tb MraY (Rv2156c) integral membrane protein and constructed the three-dimensional (3D) structure model of M.tb MraY based on homology modeling method. The validated model was complexed with antibiotic muraymycin D2 (MD2) and was used to generate structure-based pharmacophore model (e-pharmacophore). High-throughput virtual screening (HTVS) of Asinex database and molecular docking of hits was performed to identify the potential inhibitors based on their mode of interactions with the key residues involved in M.tb MraY–MD2 binding. The validation of these molecules was performed using molecular dynamics (MD) simulations for two best identified hit molecules complexed with M.tb MraY in the lipid bilayer, dipalmitoylphosphatidyl-choline (DPPC) membrane. The results indicated the stability of the complexes formed and retained non-bonding interactions similar to MD2. These findings may help in the design of new inhibitors to M.tb MraY involved in peptidoglycan biosynthesis.     

Intermolecular interactions between DNA and methamphetamine,amphetamine, ecstasy and their major metabolites

In this work, we carried out a theoretical investigation regarding amphetamine-type stimulants, which can cause central nervous system degeneration, interacting with human DNA. These include amphetamine, methamphetamine, 3,4-Methylenedioxymethamphetamine (also known as ecstasy), as well as their main metabolites. The studies were performed through molecular docking and molecular dynamics simulations, where molecular interactions of the receptor–ligand systems, along with their physical–chemical energies, were reported. Our results show that 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine (ecstasy) present considerable reactivity with the receptor (DNA), suggesting that these molecules may cause damage due to human-DNA. These results were indicated by free Gibbs change of bind (ΔG_bind) values referring to intermolecular interactions between the drugs and the minor grooves of DNA, which were predominant for all simulations. In addition, it was observed that 3,4-Dihydroxymethamphetamine (ΔG_bind = ?13.15 kcal/mol) presented greater spontaneity in establishing interactions with DNA in comparison to 3,4-Methylenedioxymethamphetamine (ΔG_bind = ?8.61 kcal/mol). Thus, according with the calculations performed our results suggest that the 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine have greater probability to provide damage to human DNA fragments.     

Microsecond Scale Replica Exchange Molecular Dynamic Simulation of Villin Headpiece: An Insight into the Folding Landscape

Abstract

Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. The development of advanced Molecular Dynamics techniques like Replica Exchange Molecular Dynamics (REMD) makes it possible to reach these experimental timescales. In this study, an attempt has been made to reach the multi microsecond simulation time scale by carrying out folding simulations on a three helix bundle protein, Villin, by combining REMD and Amber United Atom model. Twenty replicas having different temperatures ranging from 295 K to 390 K were simulated for 1.5 μs each. The lowest Root Mean Square Deviation (RMSD) structure of 2.5 Å was obtained with respect to native structure (PDB code 1VII), with all the helices formed. The folding population landscapes were built using segment-wise RMSD and Principal Components as reaction coordinates. These analyses suggest the two-stage folding for Villin. The combination of REMD and Amber United Atom model may be useful to understand the folding mechanism of various fast folding proteins