Accurate calculations of the hydration free energies of druglike molecules using the reference interaction site model

David Palmer, Volodymyr P. Sergiievskyi, Frank Jensen, Maxim V. Fedorov

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number044104
Number of pages11
JournalJournal of Chemical Physics
Volume133
Issue number4
DOIs
Publication statusPublished - 22 Jul 2010

Keywords

  • integral-equation theory
  • solvation free-energy
  • thermodynamic perturbation method
  • repulsive bridge correction
  • Ornstein-Zernike equation
  • extended rism equation
  • selective ion binding
  • 3D-RISM theory
  • force field
  • electrostatic potentials

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