Dual-Topology Hamiltonian-Replica-Exchange Overlap Histogramming Method to Calculate Relative Free Energy Difference in Rough Energy Landscape

TL;DR

This paper introduces a new overlap histogramming method using Dual-Topology Hamiltonian-Replica-Exchange to efficiently compute free energy differences in complex systems with multiple conformers and high energy barriers.

Contribution

It presents a novel methodology combining DT-HERM and overlap histogramming to improve free energy calculations in rough energy landscapes.

Findings

Successfully calculated free energy difference between Leucine and Asparagine.

Demonstrated efficiency in systems with multiple conformers and large energy barriers.

Validated the method on a challenging amino acid system.

Abstract

A novel overlap histogramming method based on Dual-Topology Hamiltonian-Replica-Exchange simulation technique is presented to efficiently calculate relative free energy difference in rough energy landscape, in which multiple conformers coexist and are separated by large energy barriers. The proposed method is based on the realization that both DT-HERM exchange efficiency and confidence of free energy determination in overlap histogramming method depend on the same criteria: neighboring states' energy derivative distribution overlap. In this paper, we demonstrate this new methodology by calculating free energy difference between amino acids: Leucine and Asparagine, which is an identified chanllenging system for free energy simulations.