The ability of the GROMOS96 force field to reproduce partition constants between water and two less polar solvents (cyclohexane and chloroform) for analogs of 18 of the 20 naturally occurring amino acids has been investigated. The estimations of the solvation free energies in water, in cyclohexane solution, and chloroform solution are based on thermodynamic integration free energy calculations ...

We present a new methodology for computing solvation free energy, which is based upon the reference interaction site model (RISM)/hypernetted chain (HNC) solvation free energy expression, but which substitutes radial distribution functions taken from simulations for those calculated by simultaneous solution of the RISM and HNC equations. Consequently, solvation free energy can be obtained from ...

Previous work describes a computational solvation model called semi-explicit assembly (SEA). The SEA water model computes the free energies of solvation of nonpolar and polar solutes in water with good efficiency and accuracy. However, SEA gives systematic errors in the solvation free energies of ions and charged solutes. Here, we describe field-SEA, an improved treatment that gives accurate so...

Differential geometry (DG) based solvation models are a new class of variational implicit solvent approaches that are able to avoid unphysical solvent-solute boundary definitions and associated geometric singularities, and dynamically couple polar and non-polar interactions in a self-consistent framework. Our earlier study indicates that DG based non-polar solvation model outperforms other meth...

Does aqueous solvent discriminate among peptide conformers? To address this question, we computed the solvation free energy of a blocked, 12-residue polyalanyl-peptide in explicit water and analyzed its solvent structure. The peptide was modeled in each of 4 conformers: alpha-helix, antiparallel beta-strand, parallel beta-strand, and polyproline II helix (P(II)). Monte Carlo simulations in the ...

Solvation effects play a profound role in the energetics of protein folding. While a continuum dielectric model of solvation may provide a sufficiently accurate estimate of the solvation effects, until now this model was too computationally expensive and unstable for folding simulations. Here we proposed a fast yet accurate and robust implementation of the boundary element solution of the Poiss...

A general expression for the distribution of the fluctuating 2(l)-pole moment M(l) of a spherical sample of dielectric material is derived on the basis of dielectric theory combined with statistical mechanics. The formulas are compared with results from computer simulations of a weakly coupled Stockmayer fluid and the agreement is shown to be excellent. Furthermore, we calculate the size of the...

Small molecule permeability through cellular membranes is critical to a better understanding of pharmacodynamics and the drug discovery endeavor. Such permeability may be estimated as a function of the free energy change of barrier crossing by invoking the barrier domain model, which posits that permeation is limited by passage through a single "barrier domain" and assumes diffusivity differenc...

Free energy potentials, combining molecular mechanics with empirical solvation and entropic terms, are used to discriminate native and near-native protein conformations from slightly misfolded decoys. Since the functional forms of these potentials vary within the field, it is of interest to determine the contributions of individual free energy terms and their combinations to the discriminative ...

We present a Ginzburg-Landau theory of solvation of ions in polar binary mixtures. The solvation free energy arising from the ion-dipole interaction can strongly depend on the composition and the ion species. Most crucial in phase separation is then the difference in the solvation free energy between the two phases, which is the origin of the Galvani potential difference known in electrochemist...