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Journal of Computer-Aided Molecular Design

, Volume 29, Issue 11, pp 1007–1014 | Cite as

A Python tool to set up relative free energy calculations in GROMACS

  • Pavel V. Klimovich
  • David L. MobleyEmail author
Article

Abstract

Free energy calculations based on molecular dynamics (MD) simulations have seen a tremendous growth in the last decade. However, it is still difficult and tedious to set them up in an automated manner, as the majority of the present-day MD simulation packages lack that functionality. Relative free energy calculations are a particular challenge for several reasons, including the problem of finding a common substructure and mapping the transformation to be applied. Here we present a tool, alchemical-setup.py, that automatically generates all the input files needed to perform relative solvation and binding free energy calculations with the MD package GROMACS. When combined with Lead Optimization Mapper (LOMAP; Liu et al. in J Comput Aided Mol Des 27(9):755–770, 2013), recently developed in our group, alchemical-setup.py allows fully automated setup of relative free energy calculations in GROMACS. Taking a graph of the planned calculations and a mapping, both computed by LOMAP, our tool generates the topology and coordinate files needed to perform relative free energy calculations for a given set of molecules, and provides a set of simulation input parameters. The tool was validated by performing relative hydration free energy calculations for a handful of molecules from the SAMPL4 challenge (Mobley et al. in J Comput Aided Mol Des 28(4):135–150, 2014). Good agreement with previously published results and the straightforward way in which free energy calculations can be conducted make alchemical-setup.py a promising tool for automated setup of relative solvation and binding free energy calculations.

Keywords

Hydration free energy Transfer free energy Free energy calculation Automated setup 

Notes

Acknowledgments

We acknowledge the financial support of the National Institutes of Health (1R15GM096257-01A1, 1R01GM108889-01) and the National Science Foundation (CHE 1352608) and computing support from the UCI GreenPlanet cluster, supported in part by NSF Grant CHE-0840513. We thank Shuai Liu (UCI) for useful comments on the LOMAP functionality, and Michael Shirts (University of Virginia) for helpful discussions.

Supplementary material

10822_2015_9873_MOESM1_ESM.zip (369 kb)
In the Supporting Information, we provide a copy of the script, as well as the input files used to set up the relative free energy calculations for a set of molecules.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity of California, IrvineIrvineUSA
  2. 2.Department of ChemistryUniversity of California, IrvineIrvineUSA

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