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...

The H-bond inventory approach is used commonly to interpret data involving changes in the number or types of protein hydrogen bonds. I point out here that this approach gives an incorrect answer either for the standard free energy or enthalpy of the reaction between simple amides and water. On the other hand, an electrostatic solvation approach fits almost within error the polar solvation free ...

Accurate prediction of hydration free energies is a key objective of any free energy method that is applied to modeling and understanding interactions in the aqueous phase. Inhomogeneous fluid solvation theory (IFST) is a statistical mechanical method for calculating solvation free energies by quantifying the effect of a solute acting as a perturbation to bulk water. IFST has found wide applica...

Simplified models and empirical potentials are being increasingly used for the analysis of proteins, frequently augmenting or replacing molecular mechanics approaches. Recent folding simulations have employed potentials that, in addition to terms assuring proper polypeptide geometry, include only two noncovalent effects-hydrogen bonding and hydrophobicity, with extremely simple approximations t...

The computational modeling of peptide inhibitors to target protein-protein binding interfaces is growing in interest as these are often too large, too shallow, and too feature-less for conventional small molecule compounds. Here, we present a rare successful application of an alchemical binding free energy method for the calculation of converged absolute binding free energies of a series of pro...

This paper applies the Bayesian Model Averaging statistical ensemble technique to estimate small molecule solvation free energies. There is a wide range of methods available for predicting solvation free energies, ranging from empirical statistical models to ab initio quantum mechanical approaches. Each of these methods is based on a set of conceptual assumptions that can affect predictive accu...