Single-Sweep Methods for Free Energy Calculations

TL;DR

This paper introduces a novel single-sweep approach combining TAMD and variational reconstruction to efficiently map multi-dimensional free energy landscapes, demonstrated on molecular systems.

Contribution

The paper presents a new method that integrates TAMD with a variational approach for accurate free energy calculations in fewer steps.

Findings

Effective in mapping free energy landscapes with fewer simulations

Comparable accuracy to established methods like metadynamics

Successfully applied to complex molecular systems like alanine dipeptide

Abstract

A simple, efficient, and accurate method is proposed to map multi-dimensional free energy landscapes. The method combines the temperature-accelerated molecular dynamics (TAMD) proposed in [Maragliano & Vanden-Eijnden, Chem. Phys. Lett. 426, 168 (2006)] with a variational reconstruction method using radial-basis functions for the representation of the free energy. TAMD is used to rapidly sweep through the important regions of the free energy landscape and compute the gradient of the free energy locally at points in these regions. The variational method is then used to reconstruct the free energy globally from the mean force at these points. The algorithmic aspects of the single-sweep method are explained in detail, and the method is tested on simple examples, compared to metadynamics, and finally used to compute the free energy of the solvated alanine dipeptide in two and four dihedral angles.