Utility of potential energy span as an approximate free energy proxy

TL;DR

This paper proposes using the span of potential energy (difference between maximum and minimum) as an efficient and more accurate proxy for free energy changes in molecular systems, based on analysis of MD simulations.

Contribution

It introduces potential energy span as a novel, computationally inexpensive proxy that correlates better with free energy changes than traditional minimum or maximum potential energy measures.

Findings

Potential energy span shows stronger correlation with free energy change.

Change in potential energy span is computationally inexpensive.

Potential energy span can serve as an effective free energy proxy.

Abstract

Free energy calculation is critical in predictive tasks such as protein folding, docking and design. However, rigorous calculation of free energy change is prohibitively expensive in these practical applications. The minimum potential energy is therefore widely utilized to approximate free energy. In this study, based on analysis of extensive molecular dynamics (MD) simulation trajectories of a few native globular proteins, we found that change of minimum and corresponding maximum potential energy terms exhibit similar level of correlation with change of free energy. More importantly, we demonstrated that change of span (maximum - minimum) of potential energy terms, which engender negligible additional computational cost, exhibit considerably stronger correlations with change of free energy than the corresponding change of minimum and maximum potential energy terms. Therefore, potential energy span may serve as an alternative efficient approximate free energy proxy.