### Abstract

We demonstrate that a new free energy functional in the integral equation theory of molecular liquids gives accurate calculations of hydration thermodynamics for drug-like molecules. The functional provides an improved description of excluded volume effects by incorporating two free coefficients. When the values of these coefficients are obtained from experimental data for simple organic molecules, the hydration free energies of an external test set of druglike molecules can be calculated with an accuracy of about 1 kcal/mol. The 3D RISM/UC method proposed here is easily implemented using existing computational software and allows in silico screening of the solvation thermodynamics of potential pharmaceutical molecules at significantly lower computational expense than explicit solvent simulations.

Language | English |
---|---|

Pages | 1423-1429 |

Number of pages | 7 |

Journal | Molecular Pharmaceutics |

Volume | 8 |

Issue number | 4 |

Early online date | 27 May 2011 |

DOIs | |

Publication status | Published - 2011 |

### Fingerprint

### Keywords

- hydration free energy
- reference interaction site model
- RISM
- solubility
- drug discovery
- RISM/UC
- bioavailability
- in silico
- virtual
- screening
- TIC - Bionanotechnology

### Cite this

*Molecular Pharmaceutics*,

*8*(4), 1423-1429. https://doi.org/10.1021/mp200119r

}

*Molecular Pharmaceutics*, vol. 8, no. 4, pp. 1423-1429. https://doi.org/10.1021/mp200119r

**Toward a universal model to calculate the solvation thermodynamics of druglike molecules : the importance of new experimental databases.** / Palmer, David; Frolov, Andrey I.; Ratkova, Ekaterina L.; Fedorov, Maxim V.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Toward a universal model to calculate the solvation thermodynamics of druglike molecules

T2 - Molecular Pharmaceutics

AU - Palmer, David

AU - Frolov, Andrey I.

AU - Ratkova, Ekaterina L.

AU - Fedorov, Maxim V.

PY - 2011

Y1 - 2011

N2 - We demonstrate that a new free energy functional in the integral equation theory of molecular liquids gives accurate calculations of hydration thermodynamics for drug-like molecules. The functional provides an improved description of excluded volume effects by incorporating two free coefficients. When the values of these coefficients are obtained from experimental data for simple organic molecules, the hydration free energies of an external test set of druglike molecules can be calculated with an accuracy of about 1 kcal/mol. The 3D RISM/UC method proposed here is easily implemented using existing computational software and allows in silico screening of the solvation thermodynamics of potential pharmaceutical molecules at significantly lower computational expense than explicit solvent simulations.

AB - We demonstrate that a new free energy functional in the integral equation theory of molecular liquids gives accurate calculations of hydration thermodynamics for drug-like molecules. The functional provides an improved description of excluded volume effects by incorporating two free coefficients. When the values of these coefficients are obtained from experimental data for simple organic molecules, the hydration free energies of an external test set of druglike molecules can be calculated with an accuracy of about 1 kcal/mol. The 3D RISM/UC method proposed here is easily implemented using existing computational software and allows in silico screening of the solvation thermodynamics of potential pharmaceutical molecules at significantly lower computational expense than explicit solvent simulations.

KW - hydration free energy

KW - reference interaction site model

KW - RISM

KW - solubility

KW - drug discovery

KW - RISM/UC

KW - bioavailability

KW - in silico

KW - virtual

KW - screening

KW - TIC - Bionanotechnology

U2 - 10.1021/mp200119r

DO - 10.1021/mp200119r

M3 - Article

VL - 8

SP - 1423

EP - 1429

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 4

ER -