Best practices in free energy calculations for drug design

Methods in Molecular Biology
Michael R Shirts

Abstract

Free energy calculations are increasingly of interest for computing biophysical properties of novel small molecules of interest in drug design, such as protein-ligand binding affinities and small molecule partition coefficients. However, these calculations are also notoriously difficult to implement correctly. In this article, we review standard methods for computing free energy differences via simulation, discuss current best practices, and examine potential pitfalls for computational researchers without extensive experience in such calculations. We include a variety of examples and tips for how to set up and conduct these calculations, including applications to relative binding affinities and absolute binding free energies.

References

May 10, 2013·Annual Review of Biophysics·John D Chodera, David L Mobley
Mar 12, 2013·Annual Review of Physical Chemistry·Riccardo Baron, J Andrew McCammon
Aug 8, 2018·Journal of Computer-aided Molecular Design·Kyungreem HanBernard R Brooks
Nov 30, 2019·Journal of Computer-aided Molecular Design·Andreas Mecklenfeld, Gabriele Raabe

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