We propose a new computational methodology that couples reference interaction site model (RISM) and molecular dynamics (MD) or Monte Carlo (MC) simulation methods for determination of solvation free energies. We employ the RISM formulation of solvation free energy. The correlation functions entering this expression are derived from radial distribution functions supplied by MD or MC simulations,...

Most proteins perform their function in aqueous solution. The interactions with water determine the stability of proteins and the desolvation costs of ligand binding or membrane insertion. However, because of experimental restrictions, absolute solvation free energies of proteins or amino acids are not available. Instead, solvation free energies are estimated based on side chain analog data. Th...

Central in a variational implicit-solvent description of biomolecular solvation is an effective free-energy functional of the solute atomic positions and the solute-solvent interface (i.e., the dielectric boundary). The free-energy functional couples together the solute molecular mechanical interaction energy, the solute-solvent interfacial energy, the solute-solvent van der Waals interaction e...

Accurate and reliable pKa prediction is of significant interest, because it provides direct information of the protonation state of a protein and can be compared to experimental data. In this work pKa shifts of three aminoacids in proteins have been calculated using molecular dynamics free energy simulations with an explicit solvent and implicit Generalized Born solvent model. The direction of ...

Building on the SVPE (surface and volume polarization for electrostatics) model for electrostatic contributions to the free energy of solvation with explicit consideration of both surface and volume polarization effects, on the SMx approach to including first-solvation-shell contributions, and on the linear relationship between the electric field and short-range electrostatic contributions foun...

Solvation free energies can now be calculated precisely from molecular simulations, providing a valuable test of the energy functions underlying these simulations. Here, we briefly review "alchemical" approaches for calculating the solvation free energies of small, neutral organic molecules from molecular simulations, and illustrate by applying them to calculate aqueous solvation free energies ...

The separation of slow nuclear and fast electronic polarization in problems related to electron mobility in polarizable media was considered by Pekar 70 years ago. Within dielectric continuum models, this separation leads to the Pekar factor in the free energy of solvation by the nuclear degrees of freedom. The main qualitative prediction of Pekar's perspective is a significant, by about a fact...

Solvation is of fundamental importance to biomolecular systems. Implicit solvent models, particularly those based on the Poisson-Boltzmann equation for electrostatic analysis, are established approaches for solvation analysis. However, ad hoc solvent-solute interfaces are commonly used in the implicit solvent theory. Recently, we have introduced differential geometry based solvation models whic...

The total free energy of a molecule includes the classical molecular mechanical energy (which is understood as the free energy in vacuum) and the solvation energy which is caused by the change of the environment of the molecule (solute) from vacuum to solvent. The solvation energy is important to the study of the inter-molecular interactions. In this paper we develop a fast surface-based genera...