Toward a universal model to calculate the solvation thermodynamics of druglike molecules: the importance of new experimental databases

David Palmer, Andrey I. Frolov, Ekaterina L. Ratkova, Maxim V. Fedorov

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

LanguageEnglish
Pages1423-1429
Number of pages7
JournalMolecular Pharmaceutics
Volume8
Issue number4
Early online date27 May 2011
DOIs
Publication statusPublished - 2011

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Thermodynamics
Databases
Pharmaceutical Preparations
Computer Simulation
Software

Keywords

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

Cite this

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title = "Toward a universal model to calculate the solvation thermodynamics of druglike molecules: the importance of new experimental databases",
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.",
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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.

In: Molecular Pharmaceutics, Vol. 8, No. 4, 2011, p. 1423-1429.

Research output: Contribution to journalArticle

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

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AU - Palmer, David

AU - Frolov, Andrey I.

AU - Ratkova, Ekaterina L.

AU - Fedorov, Maxim V.

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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

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