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Drug permeability prediction using PMF method

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Abstract

Drug permeability determines the oral availability of drugs via cellular membranes. Poor permeability makes a drug unsuitable for further development. The permeability may be estimated as the free energy change that the drug should overcome through crossing membrane. In this paper the drug permeability was simulated using molecular dynamics method and the potential energy profile was calculated with potential of mean force (PMF) method. The membrane was simulated using DPPC bilayer and three drugs with different permeability were tested. PMF studies on these three drugs show that doxorubicin (low permeability) should pass higher free energy barrier from water to DPPC bilayer center while ibuprofen (high permeability) has a lower energy barrier. Our calculation indicates that the simulation model we built is suitable to predict drug permeability.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 21103125) and China National Basic Research Program (No. 2010CB735602). MD simulations were performed on TianHe-1A supercomputer of National Supercomputing Center in Tianjin. The authors would like to thank the anonymous referees for valuable suggestions.

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Authors and Affiliations

  1. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, People’s Republic of China

    Fancui Meng

  2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, People’s Republic of China

    Fancui Meng & Weiren Xu

Authors
  1. Fancui Meng
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  2. Weiren Xu
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Correspondence to Fancui Meng.

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Meng, F., Xu, W. Drug permeability prediction using PMF method. J Mol Model 19, 991–997 (2013). https://doi.org/10.1007/s00894-012-1655-1

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  • DOI: https://doi.org/10.1007/s00894-012-1655-1

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