Best Practices for Alchemical Free Energy Calculations [Article v1.0]. Journal Article uri icon

Overview

abstract

  • Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of "bridging" potential energy functions representing alchemical intermediate states that cannot exist as real chemical species. The data collected from these bridging alchemical thermodynamic states allows the efficient computation of transfer free energies (or differences in transfer free energies) with orders of magnitude less simulation time than simulating the transfer process directly. While these methods are highly flexible, care must be taken in avoiding common pitfalls to ensure that computed free energy differences can be robust and reproducible for the chosen force field, and that appropriate corrections are included to permit direct comparison with experimental data. In this paper, we review current best practices for several popular application domains of alchemical free energy calculations performed with equilibrium simulations, in particular relative and absolute small molecule binding free energy calculations to biomolecular targets.

publication date

  • January 1, 2020

has restriction

  • bronze

Date in CU Experts

  • January 28, 2021 2:13 AM

Full Author List

  • Mey ASJS; Allen BK; Macdonald HEB; Chodera JD; Hahn DF; Kuhn M; Michel J; Mobley DL; Naden LN; Prasad S

author count

  • 15

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 2575-6524

Additional Document Info

volume

  • 2

issue

  • 1