Towards an automated pipeline for solvation free energy calculations

POSTER

Abstract

Solvation free energies are used to determine solvent effects on molecules of interest, such as the $\log P_{ow}$ of drug-like molecules. We developed MDPOW, an automated pipeline to compute solvation free energies with molecular dynamics simulations using Python and Gromacs. In order to optimize the simulation protocol, we examined the effects of varying parameters on these free energy calculations. We employed benzene as a simple test case with an known experimental hydration free energy. We varied the parameters of the MD free energy perturbation (FEP) calculations, such as temperature and pressure coupling algorithms, sampling time of the FEP windows, dispersion correction, initial conditions. We also employed two different schemes to calculate the free energy, thermodynamic integration (TI) and the Bennett acceptance ratio (BAR) method. The Coulomb component of the hydration free energy was generally insensitive to variations in parameters. The Lennard-Jones component, however, can vary by many kJ/mol and is sensitive to the temperature coupling algorithm and inconsistent initial conditions when simulations are performed in the NVT ensemble.

Authors

  • Ian Kenney

    Arizona State Univ

  • Scott D. Bergesen

    Santa Fe Institute, Arizona State University, Department of Physics and Center for Biological Physics, Arizona State University, Brigham Young University Department of Physics and Astronomy, Brigham Young University, Utah Valley University, Dixie State College, Advisor, Student, Massachusetts Institute of Technology, Thomas Jefferson National Accelerator Laboratory, Colorado College, United States Air Force Academy, Georgia Institute of Technology, Utah State University, Brigham Young University - Idaho, Utah State University- Logan, National Institute of Standards and Technology, Humboldt State University, UC Santa Cruz, Institut de Chimie des Substances Naturelles, Arizona State Univ, University of Colorado at Colorado Springs, National Jewish Health, Department of Physics, The University of Texas at Austin, Department of Physics, New Mexico State University, U. S. Air Force Academy, Brigham Young Univ - Provo, University of New South Wales, University of Texas, University of Warwick, University of Louisiana, Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, USA., Center for Materials Genomics, Department of Mechanical Engineering and Materials Science and Department of Physics, Duke University, Durham, North Ca, Duke University, Durham, North Carolina., Brigham Young University -- Provo, Utah, General Atomics -- San Diego, California, Department of Mathematics, University of British Columbia, Department of Physics, Arizona State University, UC Riverside, UMASS, STScI, NOAO, UT Austin, Texas A&M, Arizona State Univeristy, New Mexico State Univ, Los Alamos National Laboratory, Colorado State Univ, Department of Physics, Oregon State University, Colorado School of Mines, University of Alaska, Fairbanks, The Peac Institute of Multiscale Modeling, UNSW Canberra

  • Scott D. Bergesen

    Santa Fe Institute, Arizona State University, Department of Physics and Center for Biological Physics, Arizona State University, Brigham Young University Department of Physics and Astronomy, Brigham Young University, Utah Valley University, Dixie State College, Advisor, Student, Massachusetts Institute of Technology, Thomas Jefferson National Accelerator Laboratory, Colorado College, United States Air Force Academy, Georgia Institute of Technology, Utah State University, Brigham Young University - Idaho, Utah State University- Logan, National Institute of Standards and Technology, Humboldt State University, UC Santa Cruz, Institut de Chimie des Substances Naturelles, Arizona State Univ, University of Colorado at Colorado Springs, National Jewish Health, Department of Physics, The University of Texas at Austin, Department of Physics, New Mexico State University, U. S. Air Force Academy, Brigham Young Univ - Provo, University of New South Wales, University of Texas, University of Warwick, University of Louisiana, Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, USA., Center for Materials Genomics, Department of Mechanical Engineering and Materials Science and Department of Physics, Duke University, Durham, North Ca, Duke University, Durham, North Carolina., Brigham Young University -- Provo, Utah, General Atomics -- San Diego, California, Department of Mathematics, University of British Columbia, Department of Physics, Arizona State University, UC Riverside, UMASS, STScI, NOAO, UT Austin, Texas A&M, Arizona State Univeristy, New Mexico State Univ, Los Alamos National Laboratory, Colorado State Univ, Department of Physics, Oregon State University, Colorado School of Mines, University of Alaska, Fairbanks, The Peac Institute of Multiscale Modeling, UNSW Canberra