## 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 language | English |
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Article number | 044104 |

Number of pages | 11 |

Journal | Journal of Chemical Physics |

Volume | 133 |

Issue number | 4 |

DOIs | |

Publication status | Published - 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