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Ab initio quantum mechanics-based free energy perturbation method for calculating relative solvation free energies



Ab initio quantum mechanics-based free energy perturbation method for calculating relative solvation free energies



Journal of Computational Chemistry 28(2): 491-494



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.

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Accession: 048140648

Download citation: RISBibTeXText

PMID: 17186484

DOI: 10.1002/jcc.20510


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