Accurate calculations of the hydration free energies of druglike molecules using the reference interaction site model.
We report on the results of testing the reference interaction site model (RISM) for the estimation of the hydration free energy of druglike molecules. The optimum model was selected after testing of different RISM free energy expressions combined with different quantum mechanics and empirical force-field methods of structure optimization and atomic partial charge calculation. The final model gave a systematic error with a standard deviation of 2.6 kcal/mol for a test set of 31 molecules selected from the SAMPL1 blind challenge set [J. P. Guthrie, J. Phys. Chem. B 113, 4501 (2009)]. After parametrization of this model to include terms for the excluded volume and the number of atoms of different types in the molecule, the root mean squared error for a test set of 19 molecules was less than 1.2 kcal/mol.
Palmer
David S
DS
Max Planck Institute for the Mathematics in the Sciences, Inselstrasse 22, DE-04103 Leipzig, Germany.
Sergiievskyi
Volodymyr P
VP
Jensen
Frank
F
Fedorov
Maxim V
MV
D000465:Algorithms; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011789:Quantum Theory; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water