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Ab initio quantum mechanics‐based free energy perturbation method for calculating relative solvation free energies
Author(s) -
Reddy M. Rami,
Singh U. C.,
Erion Mark D.
Publication year - 2006
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20510
Subject(s) - solvation , ab initio , free energy perturbation , perturbation theory (quantum mechanics) , quantum , force field (fiction) , molecule , chemistry , computational chemistry , perturbation (astronomy) , statistical physics , physics , quantum mechanics , molecular dynamics
A free energy perturbation (FEP) method was developed that uses ab initio quantum mechanics (QM) for treating the solute molecules and molecular mechanics (MM) for treating the surroundings. Like our earlier results using AM1 semi empirical QMs, the ab initio QM/MM‐based FEP method was shown to accurately calculate relative solvation free energies for a diverse set of small molecules that differ significantly in structure, aromaticity, hydrogen bonding potential, and electron density. Accuracy was similar to or better than conventional FEP methods. The QM/MM‐based methods eliminate the need for time‐consuming development of MM force field parameters, which are frequently required for drug‐like molecules containing structural motifs not adequately described by MM. Future automation of the method and parallelization of the code for Linux 128/256/512 clusters is expected to enhance the speed and increase its use for drug design and lead optimization. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 491–494, 2007