Best practices in free energy calculations for drug design. Journal Article uri icon



  • 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.

publication date

  • January 1, 2012

has subject area

has restriction

  • closed

Date in CU Experts

  • September 4, 2015 2:15 AM

Full Author List

  • Shirts MR

author count

  • 1

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 1940-6029

Additional Document Info

start page

  • 425

end page

  • 467


  • 819