## Abstract

The three-dimensional reference interaction site model (3D-RISM) theory, which is one of the most applicable integral equation theories for molecular liquids, overestimates the absolute values of solvation-free-energy (SFE) for large solute molecules in water. To improve the free-energy density functional for the SFE of solute molecules, we propose a reference-modified density functional theory (RMDFT) that is a general theoretical approach to construct the free-energy density functional systematically. In the RMDFT formulation, hard-sphere (HS) fluids are introduced as the reference system instead of an ideal polyatomic molecular gas, which has been regarded as the appropriate reference system of the interaction-site-model density functional theory for polyatomic molecular fluids. We show that using RMDFT with a reference HS system can significantly improve the absolute values of the SFE for a set of neutral amino acid side-chain analogues as well as for 504 small organic molecules.

Original language | English |
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Pages (from-to) | 1359-1369 |

Number of pages | 11 |

Journal | Journal of Computational Chemistry |

Volume | 36 |

Issue number | 18 |

DOIs | |

Publication status | Published - Jul 1 2015 |

## Keywords

- 3D-RISM theory
- amino acid side-chain
- chignolin
- classical density functional theory
- salvation-free-energy
- water

## ASJC Scopus subject areas

- Chemistry(all)
- Computational Mathematics