Free energy calculation of a molecule by removing VDW and Coulomb interactions in a transformation and treating the molecule as non interacting systems

TL;DR

This paper introduces a simplified method for calculating free energies in molecular systems by removing VDW and Coulomb interactions, treating molecules as non-interacting, which significantly speeds up computations while maintaining accuracy.

Contribution

The paper presents a novel approach to free energy calculation that simplifies the process by removing specific interactions and treating molecules as non-interacting systems, applicable in various environments.

Findings

Method agrees with MD simulations in vacuum and water.

Significantly faster computation, up to 10^12 times faster.

Applicable to molecules in different environments.

Abstract

Free energy calculations in molecular simulations have a variety of applications including determining the strength of molecular processes such as solvation and binding. It has been recently shown that when removing the VDW and Coulomb potential terms of a group of atoms in a molecule by performing a transformation, the molecule can be treated as non interacting systems in the free energy calculation. This treatment is applicable both when the molecule is in vacuum and in liquid and enables a very simple calculation of the free energies associated with the potentials that depend on the relative spherical coordinates of these atoms. Here we demonstrate the method in the free energy calculation of a Methanethiol molecule and compare the results to these obtained by MD simulations in vacuum and in water. The comparison shows agreement between the results and faster computation when using the method by factors varying between 5000 and 10^(12) for the same computational resources.