Polarizable coarse-grained models for molecular dynamics simulation of liquid cyclohexane.

Force field parameters for polarizable coarse-grained (CG) supra-atomic models of liquid cyclohexane are proposed. Two different bead sizes were investigated, one representing two fine-grained (FG) CH(2)r united atoms of the cyclohexane ring, and one representing three FG CH(2)r united atoms. Electronic polarizability is represented by a massless charge-on-spring particle connected to each CG bead. The model parameters were calibrated against the experimental density and heat of vaporization of liquid cyclohexane, and the free energy of cyclohexane hydration. Both models show good agreement with thermodynamic properties of cyclohexane, yet overestimate the self-diffusion. The dielectric properties of the polarizable models agree very well with experiment.

A polarizable empirical force field for molecular dynamics simulation of liquid hydrocarbons.

Electronic polarizability is usually treated implicitly in molecular simulations, which may lead to imprecise or even erroneous molecular behavior in spatially electronically inhomogeneous regions of systems such as proteins, membranes, interfaces between compounds, or mixtures of solvents. The majority of available molecular force fields and molecular dynamics simulation software packages does not account explicitly for electronic polarization. Even the simplest charge-on-spring (COS) models have only been developed for few types of molecules. In this work, we report a polarizable COS model for cyclohexane, as this molecule is a widely used solvent, and for linear alkanes, which are also used as solvents, and are the precursors of lipids, amino acid side chains, carbohydrates, or nucleic acid backbones. The model is an extension of a nonpolarizable united-atom model for alkanes that had been calibrated against experimental values of the density, the heat of vaporization and the Gibbs free energy of hydration for each alkane. The latter quantity was used to calibrate the parameters governing the interaction of the polarizable alkanes with water. Subsequently, the model was tested for other structural, thermodynamic, dielectric, and dynamic properties such as trans/gauche ratios, excess free energy, static dielectric permittivity, and self-diffusion. A good agreement with the experimental data for a large set of properties for each considered system was obtained, resulting in a transferable set of polarizable force-field parameters for CH2, CH3, and CH4 moieties.

Receptor concentration and diffusivity control multivalent binding of Sv40 to membrane bilayers.

Incoming Simian Virus 40 particles bind to their cellular receptor, the glycolipid GM1, in the plasma membrane and thereby induce membrane deformation beneath the virion leading to endocytosis and infection. Efficient membrane deformation depends on receptor lipid structure and the organization of binding sites on the internalizing particle. To determine the role of receptor diffusion, concentration and the number of receptors required for stable binding in this interaction, we analyze the binding of SV40 to GM1 in supported membrane bilayers by computational modeling based on experimental data. We measure the diffusion rates of SV40 virions in solution by fluorescence correlation spectroscopy and of the receptor in bilayers by single molecule tracking. Quartz-crystal microbalance with dissipation (QCM-D) is used to measure binding of SV40 virus-like particles to bilayers containing the viral receptor GM1. We develop a phenomenological stochastic dynamics model calibrated against this data, and use it to investigate the early events of virus attachment to lipid membranes. Our results indicate that SV40 requires at least 4 attached receptors to achieve stable binding. We moreover find that receptor diffusion is essential for the establishment of stable binding over the physiological range of receptor concentrations and that receptor concentration controls the mode of viral motion on the target membrane. Our results provide quantitative insight into the initial events of virus-host interaction at the nanoscopic level.

Flexible Boundaries for Multiresolution Solvation: An Algorithm for Spatial Multiscaling in Molecular Dynamics Simulations.

An algorithm is proposed for performing molecular dynamics (MD) simulations of a biomolecular solute represented at atomistic resolution surrounded by a surface layer of atomistic fine-grained (FG) solvent molecules within a bulk represented by coarse-grained (CG) solvent beads. The method, called flexible boundaries for multiresolution solvation (FBMS), is based on: (i) a three-region layering of the solvent around the solute, involving an FG layer surrounded by a mixed FG-CG buffer layer, itself surrounded by a bulk CG region; (ii) a definition of the layer boundary that relies on an effective distance to the solute surface and is thus adapted to the shape of the solute as well as adjusts to its conformational changes. The effective surface distance is defined by inverse-nth power averaging over the distances to all non-hydrogen solute atoms, and the layering is enforced by means of half-harmonic distance restraints, attractive for the FG molecules and repulsive for the CG beads. A restraint-free region at intermediate distances enables the formation of the buffer layer, where the FG and CG solvents can mix freely. The algorithm is tested and validated using the GROMOS force field and the associated FG (SPC) and CG (polarizable CGW) water models. The test systems include pure-water systems, where one FG molecule plays the role of a solute, and a deca-alanine peptide with two widely different solute shapes considered, α-helical and fully extended. In particular, as the peptide unfolds, the number of FG molecules required to fill its close-range solvation layer increases, with the additional molecules being provided by the buffer layer. Further validation involves simulations of four proteins in multiresolution FG/CG mixtures. The resulting structural, energetic, and solvation properties are found to be similar to those observed in corresponding pure FG simulations.