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An atomistic model of passive membrane permeability: application to a series of FDA approved drugs

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Abstract

We apply an atomistic model of passive membrane permeability to a series of weakly basic drugs. The computational model uses conformational sampling in combination with an all-atom force field and implicit solvent model to estimate relative passive membrane permeabilities. The model does not require the use of training data for rank-ordering compounds, and as such represents a different approach from the more commonly employed QSPR models. We compare the computational results to previously published experimental PAMPA and Caco-2 permeabilities.

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Acknowledgments

This work was supported by NIH grant AI035707. MPJ is a consultant to Schrödinger, Inc.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, UCSF, San Francisco, CA, 94158-2517, USA

    Chakrapani Kalyanaraman & Matthew P. Jacobson

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  1. Chakrapani Kalyanaraman
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  2. Matthew P. Jacobson
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Correspondence to Matthew P. Jacobson.

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Kalyanaraman, C., Jacobson, M.P. An atomistic model of passive membrane permeability: application to a series of FDA approved drugs. J Comput Aided Mol Des 21, 675–679 (2007). https://doi.org/10.1007/s10822-007-9141-z

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  • DOI: https://doi.org/10.1007/s10822-007-9141-z

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