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Using membrane partitioning simulations to predict permeability of forty-nine drug-like molecules

Dickson, Callum and Hornak, Viktor and Bednarczyk, Dallas and Duca, Jose (2018) Using membrane partitioning simulations to predict permeability of forty-nine drug-like molecules. Journal of Chemical Information and Modeling. ISSN 1549-95961549-960X

Abstract

A simple descriptor calculated from molecular dynamics simulations of the membrane partitioning event is found to correlate well with experimental measurements of membrane permeation from the high throughput MDCK-LE assay using a dataset of 49 drug-like molecules. This descriptor approximates the enthalpy cost to membrane flip-flop, which for many molecules limits permeability. Performance is found to be superior in comparison to calculated properties such as clogP, clogD or PSA. Furthermore, the atomistic simulations provide a structural understanding of the partitioned drug membrane complex, facilitating medicinal chemistry optimization of membrane permeability.

Item Type: Article
Date Deposited: 26 Dec 2018 00:45
Last Modified: 26 Dec 2018 00:45
URI: https://oak.novartis.com/id/eprint/37959

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