Free Energy Calculations by Computer Simulation

TLDR

Solvation critically influences molecular properties, yet its role remains challenging to quantify in chemistry and biochemistry. Using advanced statistical mechanical theory and molecular dynamics on supercomputers, the authors compute solvation free energies for all amino acid side chains, four nucleic acid bases, and other organic molecules. The calculated solvation free energies enable prediction of the effect of a site‑specific mutation on trypsin stability, with results agreeing well with experiments.

Abstract

A fundamental problem in chemistry and biochemistry is understanding the role of solvation in determining molecular properties. Recent advances in statistical mechanical theory and molecular dynamics methodology can be used to solve this problem with the aid of supercomputers. By using these advances the free energies of solvation of all the chemical classes of amino acid side chains, four nucleic acid bases and other organic molecules can be calculated. The effect of a site-specific mutation on the stability of trypsin is predicted. The results are in good agreement with available experiments.