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J Comput Chem. 2017 Sep 5;38(23):2047-2055. doi: 10.1002/jcc.24853. Epub 2017 Jun 10.

Tinker-OpenMM: Absolute and relative alchemical free energies using AMOEBA on GPUs.

Author information

1
Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, 78712.
2
Department of Chemistry, Washington University in St. Louis, St. Louis, Missouri, 63130.
3
Division of Chemical Biology and Medicinal Chemistry, University of Texas at Austin, Austin, Texas, 78712.
4
Institut des Sciences du Calcul et des Données, UPMC Université Paris 06, F-75005, Paris, France.
5
Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC, UMR7616 CNRS, Paris, France.
6
Institut Universitaire de France, Paris Cedex 05, 75231, France.

Abstract

The capabilities of the polarizable force fields for alchemical free energy calculations have been limited by the high computational cost and complexity of the underlying potential energy functions. In this work, we present a GPU-based general alchemical free energy simulation platform for polarizable potential AMOEBA. Tinker-OpenMM, the OpenMM implementation of the AMOEBA simulation engine has been modified to enable both absolute and relative alchemical simulations on GPUs, which leads to a ∼200-fold improvement in simulation speed over a single CPU core. We show that free energy values calculated using this platform agree with the results of Tinker simulations for the hydration of organic compounds and binding of host-guest systems within the statistical errors. In addition to absolute binding, we designed a relative alchemical approach for computing relative binding affinities of ligands to the same host, where a special path was applied to avoid numerical instability due to polarization between the different ligands that bind to the same site. This scheme is general and does not require ligands to have similar scaffolds. We show that relative hydration and binding free energy calculated using this approach match those computed from the absolute free energy approach.

KEYWORDS:

AMOEBA; OpenMM; Tinker; free energy calculation; graphics processing units

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