CHARMM-GUI Free Energy Calculator for Absolute and Relative Ligand Solvation and Binding Free Energy Simulations

Kim, Seonghoon; Oshima, Hiraku; Zhang, Han; Kern, Nathan R.; Re, Suyong; Lee, Jumin; Roux, Benoît; Sugita, Yuji; Jiang, Wei; Im, Wonpil

doi:10.1021/acs.jctc.0c00884

Title: CHARMM-GUI Free Energy Calculator for Absolute and Relative Ligand Solvation and Binding Free Energy Simulations

Journal Article · Wed Oct 28 00:00:00 EDT 2020 · Journal of Chemical Theory and Computation

DOI:https://doi.org/10.1021/acs.jctc.0c00884· OSTI ID:1774599

Kim, Seonghoon ^[1];

^[2]; Zhang, Han ^[1]; Kern, Nathan R. ^[1]; Re, Suyong ^[2];

^[1];

^[3];

^[4]; Jiang, Wei ^[5];

^[6]

Lehigh Univ., Bethlehem, PA (United States)
RIKEN Center for Biosystems Dynamics Research, Kobe (Japan)
Univ. of Chicago, IL (United States)
RIKEN Center for Biosystems Dynamics Research, Kobe (Japan); RIKEN Center for Computational Science, Kobe (Japan); RIKEN Cluster for Pioneering Research, Wako (Japan)
Argonne National Lab. (ANL), Argonne, IL (United States). Argonne Leadership Computing Facility (ALCF)
Lehigh Univ., Bethlehem, PA (United States); Korea Inst. for Advanced Study, Seoul (Korea, Republic of)

Alchemical free energy simulations have long been utilized to predict free energy changes for binding affinity and solubility of small molecules. However, while the theoretical foundation of these methods is well established, seamlessly handling many of the practical aspects regarding the preparation of the different thermodynamic end states of complex molecular systems and the numerous processing scripts often remains a burden for successful applications. Here, we present CHARMM-GUI Free Energy Calculator (http://www.charmm-gui.org/input/fec) that provides various alchemical free energy perturbation molecular dynamics (FEP/MD) systems with input and post-processing scripts for NAMD and GENESIS. Four submodules are available: Absolute Ligand Binder (for absolute ligand binding FEP/MD), Relative Ligand Binder (for relative ligand binding FEP/MD), Absolute Ligand Solvator (for absolute ligand solvation FEP/MD), and Relative Ligand Solvator (for relative ligand solvation FEP/MD). Each module is designed to build multiple systems of a set of selected ligands at once for high-throughput FEP/MD simulations. The capability of Free Energy Calculator is illustrated by absolute and relative solvation FEP/MD of a set of ligands and absolute and relative binding FEP/MD of a set of ligands for T4-lysozyme in solution and the adenosine A_2A receptor in a membrane. The calculated free energy values are overall consistent with the experimental and published free energy results (within ~1 kcal/mol). We hope that Free Energy Calculator is useful to carry out high-throughput FEP/MD simulations in the field of biomolecular sciences and drug discovery.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Argonne Leadership Computing Facility (ALCF)

Sponsoring Organization:: USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR); National Science Foundation (NSF); National Institutes of Health (NIH); Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)

Grant/Contract Number:: AC02-06CH11357; MCB-1810695; DBI-1660380; MCB-1517221; GM138472; P41-GM104601; 19H05645

OSTI ID:: 1774599

Journal Information:: Journal of Chemical Theory and Computation, Vol. 16, Issue 11; ISSN 1549-9618

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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