Improving the Prediction of Absolute Solvation Free Energies Using the Next Generation OPLS Force Field

Devleena Shivakumar; Edward Harder; Wolfgang Damm; Richard A Friesner; Woody Sherman

doi:10.1021/ct300203w

Improving the Prediction of Absolute Solvation Free Energies Using the Next Generation OPLS Force Field

J Chem Theory Comput. 2012 Aug 14;8(8):2553-8. doi: 10.1021/ct300203w. Epub 2012 Jul 9.

Authors

Devleena Shivakumar¹, Edward Harder¹, Wolfgang Damm¹, Richard A Friesner², Woody Sherman¹

Affiliations

¹ Schrödinger, Inc., 120 West 45th Street, 17th Floor, New York, New York 10036, United States.
² Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, United States.

PMID: 26592101
DOI: 10.1021/ct300203w

Abstract

Explicit solvent molecular dynamics free energy perturbation simulations were performed to predict absolute solvation free energies of 239 diverse small molecules. We use OPLS2.0, the next generation OPLS force field, and compare the results with popular small molecule force fields-OPLS_2005, GAFF, and CHARMm-MSI. OPLS2.0 produces the best correlation with experimental data (R(2) = 0.95, slope = 0.96) and the lowest average unsigned errors (0.7 kcal/mol). Important classes of compounds that performed suboptimally with OPLS_2005 show significant improvements.