Guidelines for the analysis of free energy calculations

Journal of Computer-aided Molecular Design
Pavel V KlimovichDavid L Mobley


Free energy calculations based on molecular dynamics simulations show considerable promise for applications ranging from drug discovery to prediction of physical properties and structure-function studies. But these calculations are still difficult and tedious to analyze, and best practices for analysis are not well defined or propagated. Essentially, each group analyzing these calculations needs to decide how to conduct the analysis and, usually, develop its own analysis tools. Here, we review and recommend best practices for analysis yielding reliable free energies from molecular simulations. Additionally, we provide a Python tool,, freely available on GitHub as part of the pymbar package (located at, that implements the analysis practices reviewed here for several reference simulation packages, which can be adapted to handle data from other packages. Both this review and the tool covers analysis of alchemical calculations generally, including free energy estimates via both thermodynamic integration and free energy perturbation-based estimators. Our Python tool also handles output from multiple types of free energy calculations, including expanded ensemble and Hamilto...Continue Reading


Jan 13, 2016·The Journal of Physical Chemistry. B·Maksim MisinDavid S Palmer
Jan 6, 2016·Journal of Chemical Theory and Computation·Xiangyu JiaYe Mei
Jan 3, 2016·The Journal of Chemical Physics·M N MeloS J Marrink
Dec 23, 2015·Advances in Bioinformatics·Igor V OferkinVladimir B Sulimov
Jan 2, 2016·The Journal of Physical Chemistry Letters·Shun SakurabaTomoshi Kameda
Oct 22, 2015·Journal of Computer-aided Molecular Design·Pavel V Klimovich, David L Mobley
May 2, 2016·The Journal of Chemical Physics·Erich R KuechlerDarrin M York
May 20, 2016·International Journal of Molecular Sciences·Nusret Duygu Yilmazer, Martin Korth
Jul 20, 2016·Journal of Chemical Theory and Computation·Caitlin C BannanDavid L Mobley
Jul 23, 2016·The Journal of Physical Chemistry. B·Amandeep K SanghaJeremy C Smith
Sep 8, 2016·The Journal of Physical Chemistry. B·J Wesley BarnettHenry S Ashbaugh
Sep 30, 2016·Journal of Computer-aided Molecular Design·Caitlin C BannanDavid L Mobley
Nov 18, 2016·Physical Chemistry Chemical Physics : PCCP·Stefania EvoliBruno Rizzuti
Dec 24, 2016·Journal of the American Chemical Society·Matteo AldeghiPhilip C Biggin
Feb 9, 2017·The Journal of Physical Chemistry. B·Reinier L C Akkermans
Feb 9, 2017·Proteins·Govardhan A BalajiShashidhar N Rao
Mar 1, 2017·The Journal of Physical Chemistry. B·Josh V VermaasEmad Tajkhorshid
Apr 2, 2017·Journal of Computer-aided Molecular Design·A F Marmolejo-Valencia, K Martínez-Mayorga
Jan 20, 2017·Journal of Computational Chemistry·You XuLennart Nilsson
Jan 25, 2017·Physical Chemistry Chemical Physics : PCCP·Srinivasa M GopalLars V Schäfer
May 31, 2017·Physical Chemistry Chemical Physics : PCCP·Zhao X SunJohn Z H Zhang
Jul 18, 2017·Physical Chemistry Chemical Physics : PCCP·Sehee NaThorsten Koslowski
Mar 14, 2018·Journal of Computational Chemistry·Daniel J MermelsteinRoss C Walker
Sep 5, 2018·Physical Chemistry Chemical Physics : PCCP·Pu DuRevati Kumar
Oct 12, 2018·Journal of Computational Chemistry·Sehee NaThorsten Koslowski
Feb 15, 2019·Journal of Computational Chemistry·Xiaohui WangZhaoxi Sun
Mar 7, 2019·Physical Chemistry Chemical Physics : PCCP·Jörg BazNiels Hansen
Mar 12, 2019·Physical Chemistry Chemical Physics : PCCP·Xiaohui WangZhaoxi Sun
Mar 22, 2019·Physical Chemistry Chemical Physics : PCCP·Xiaohui Wang, Zhaoxi Sun
Jun 25, 2019·Physical Chemistry Chemical Physics : PCCP·Zhaoxi SunQiaole He
Jul 26, 2019·Journal of Computational Chemistry·Shuntaro ChibaMitsunori Ikeguchi
Nov 5, 2019·Physical Chemistry Chemical Physics : PCCP·Jerônimo LameiraCarlos A Montanari
Oct 2, 2019·International Journal of Molecular Sciences·Song XueZheng Zheng
Dec 25, 2019·Biochemical Society Transactions·Robin A CoreyMark S P Sansom
Dec 25, 2019·Physical Chemistry Chemical Physics : PCCP·Zhaoxi SunJohn Z H Zhang
Nov 30, 2019·Journal of Computer-aided Molecular Design·Andreas Mecklenfeld, Gabriele Raabe
Sep 6, 2018·Current Medicinal Chemistry·Vladimir B SulimovAlexey V Sulimov
May 26, 2020·Journal of Computational Chemistry·Yoshiaki Tanida, Azuma Matsuura
Jul 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vladimir P BerishviliVladimir A Palyulin


Jan 1, 1989·Annual Review of Biophysics and Biophysical Chemistry·D L Beveridge, F M DiCapua
Nov 26, 1999·Nature·P E MarszalekJ M Fernandez
Dec 11, 2007·The Journal of Chemical Physics·Thomas SteinbrecherDavid A Case
Jun 17, 2008·The Journal of Physical Chemistry. B·Francisco J Martínez-Veracoechea, Fernando A Escobedo
Dec 3, 2008·The Journal of Chemical Physics·Michael R Shirts, John D Chodera
Jan 17, 2009·The Journal of Physical Chemistry. B·Yuqing Deng, Benoît Roux
Sep 29, 2009·Journal of Molecular Biology·Sarah E BoyceBrian K Shoichet
Feb 13, 2010·Journal of Chemical Theory and Computation·David L MobleyKen A Dill
Apr 8, 2010·Journal of Computer-aided Molecular Design·Pavel V Klimovich, David L Mobley
Aug 13, 2010·The Journal of Physical Chemistry. B·Andrew PohorilleChristophe Chipot
Jul 27, 2011·The Journal of Chemical Physics·Tri T Pham, Michael R Shirts
Sep 29, 2011·Journal of Computational Chemistry·Floris P Buelens, Helmut Grubmüller
Mar 13, 2014·Journal of Computer-aided Molecular Design·Jacob I Monroe, Michael R Shirts
Jul 10, 2012·Journal of Chemical Theory and Computation·Vytautas GapsysBert L de Groot
Dec 13, 2011·Journal of Chemical Theory and Computation·Himanshu Paliwal, Michael R Shirts
Sep 13, 2011·Journal of Chemical Theory and Computation·Andrew S PaluchEdward J Maginn
May 11, 2010·Journal of Chemical Theory and Computation·Devleena ShivakumarWoody Sherman
Jan 1, 2007·Journal of Chemical Theory and Computation·John D ChoderaKen A Dill

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