A surface-integral model for log P OW

Journal of Chemical Information and Modeling
Christian KramerTimothy Clark

Abstract

Log P(OW), the negative logarithm of the octanol-water partition coefficient, is omnipresent in computational drug design. Here, we present a surface-integral model for calculating log P(OW). The model is based on local properties calculated using AM1 semiempirical molecular orbital theory. These are the molecular electrostatic potential (MEP), local ionization energy (IE(L)), local electron affinity (EA(L)), local hardness (HARD), local polarizability (POL), and the local field normal to the surface (FN). We have developed a new scheme to calculate a local hydrophobicity based on binning the range of local surface properties instead of using polynomial expansions of the base terms. The model has been trained using approximately 9500 compounds available from the literature. It was validated on approximately 1350 compounds from the literature and an in-house validation set of 768 compounds from Boehringer-Ingelheim. The model performs similarly to or slightly better than the best commercially available models. We also introduce a model based purely on conformationally rigid compounds that performs well for flexible compounds if the Boltzmann weighted predictions for the different conformers are used. This is the first 3D QSPR mo...Continue Reading

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Citations

Nov 24, 2011·Journal of Computer-aided Molecular Design·Markus MuehlbacherJohannes Kornhuber
Jun 1, 2011·Journal of Chemical Information and Modeling·Christian Kramer, Peter Gedeck
Aug 17, 2011·Journal of Chemical Information and Modeling·Markus MuehlbacherTimothy Clark
Jun 29, 2011·Future Medicinal Chemistry·Giulio VistoliBernard Testa
Jun 29, 2014·Journal of Molecular Modeling·Bernd Beck, Tim Geppert
Mar 30, 2010·Journal of Computer-aided Molecular Design·Timothy Clark
Jan 12, 2010·Journal of Molecular Modeling·Timothy Clark
Jan 22, 2010·Journal of Chemical Information and Modeling·Christian KramerTimothy Clark

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