Calculation of molecular free energies in classical potentials

TL;DR

This paper introduces a new classical potential-based method for accurately calculating molecular free energies by transforming molecules and analytically or numerically computing free energy differences, applicable to large molecules and reactions.

Contribution

A novel two-step classical potential method for calculating molecular free energies that overcomes limitations of quantum and harmonic approximations.

Findings

Method accurately computes free energies of large molecules.

Applicable to free energy differences in complex environments.

Potential use in simulating chemical reactions.

Abstract

Free energies of molecules can be calculated by quantum computations or by normal mode classical calculations. However, the first can be computationally impractical for large molecules and the second is based on the assumption of harmonic dynamics. We present a novel, accurate and complete calculation of molecular free energies in standard classical potentials. In this method we transform the molecule by relaxing potential terms which depend on the coordinates of a group of atoms in that molecule and calculate the free energy difference associated with the transformation. Then, since the transformed molecule can be treated as non interacting systems, the free energy associated with these atoms is analytically or numerically calculated. This two-step calculation can be applied to calculate free energies of molecules or free energy difference between (possibly large) molecules in a general environment. We suggest the potential application of free energy calculation of chemical reactions in classical molecular simulations.