Force switching and potential shifting lead to significant cutoff dependence in alchemical free energies

TL;DR

This paper investigates how different methods for handling long-range interactions in molecular simulations affect the accuracy of free energy calculations, revealing that some methods are cutoff-independent while others introduce significant cutoff dependence.

Contribution

The study systematically compares the effects of force switching, potential shifting, and Ewald summation on free energy accuracy across various molecular systems.

Findings

Potential switching and particle-mesh Ewald yield cutoff-independent free energies.

Force switching and potential shifting cause significant cutoff dependence.

Long-range energy treatment methods impact the reliability of free energy calculations.

Abstract

The accurate treatment of long-range energy terms such as van der Waals interactions is crucial for reliable free energy calculations in molecular simulations. Methods like force switching, potential switching, potential shifting, and Ewald summation of van der Waals are commonly employed to smooth the truncation or otherwise manage these interactions at and beyond a cutoff distance, but their effects on free energy calculations are not always clear. In this study, we systematically explore the effects of these modifiers on the accuracy of free energy calculations using model systems: Lennard-Jones spheres, all-atom anthracene in water with GROMACS, and alkane chains in water with LAMMPS. Our results reveal that free energies of solvation using potential switching and particle-mesh Ewald summation of long-range Lennard-Jones are essentially independent of cutoff in solution, while force switching and potential shifting introduce cutoff-dependent behavior significant enough to affect the utility of the calculations.