Entropic measure to prevent energy over-minimization in molecular dynamics simulations

TL;DR

This paper investigates how excessive energy minimization in molecular dynamics can distort protein structures by increasing entropy, and proposes an entropic measure to optimize minimization steps for maintaining near-native conformations.

Contribution

It introduces a Pareto front-based entropic measure to assess and prevent over-minimization in protein energy minimization processes.

Findings

Over-minimization increases protein entropy and diverges structures from native states.

The proposed measure helps select optimal minimization steps.

Using the measure preserves near-native protein conformations.

Abstract

This work examines the impact of energy over-minimization on an ensemble of biological molecules subjected to the potential energy minimization procedure in vacuum. In the studied structures, long potential energy minimization stage leads to an increase of the main- and side-chain entropies in proteins. We show that such over-minimization may diverge the protein structures from the near-native attraction basin which possesses a minimum of free energy. We propose a measure based on the Pareto front of total entropy for quality assessment of minimized protein conformation. This measure may help in selection of adequate number of energy minimization steps in protein modelling and, thus, in preservation of the near-native protein conformation.