Volume Determination of Globular Proteins by Molecular Dynamics

TL;DR

This paper demonstrates that molecular dynamics simulations can accurately determine the molar volumes of globular proteins, including effects of amino acid substitutions, providing a computationally feasible alternative to experimental methods.

Contribution

The study introduces a molecular dynamics approach for volume determination of proteins that accurately reproduces experimental data and captures volumetric effects of amino acid mutations.

Findings

Simulations match experimental molar volumes

Amino acid substitutions cause expected volumetric changes

Method is feasible with modern computational resources

Abstract

Molecular dynamics simulations of myoglobin and aspartate aminotransferase, with explicit solvent, are shown to accurately reproduce the experimentally measured molar volumes. Single amino-acid substitution at VAL39 of aspartate aminotransferase is known to produce large volumetric changes in the enzyme, and this effect is demonstrated in simulation as well. This molecular dynamics approach, while more computationally expensive that extant computational methods of determining the apparent volume of biological systems, is quite feasible with modern computer hardware and is shown to yield accurate volumetric data with as little as several nanoseconds of dynamics.