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The ability of molecular docking to unravel the controversy and challenges related to P-glycoprotein—a well-known, yet poorly understood drug transporter

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Summary

P-glycoprotein is the most crucial membrane transporter implicated in tumor resistance. Intensive efforts were paid to elucidate the complex mechanism of transport and to identify modulators of this transporter. However, the borderline between substrates and modulators is very thin and identification of the binding sites within P-glycoprotein is complex. Herein, we provide an intensive review of those issues and use molecular docking to assess its ability: first, to differentiate between three groups (substrates, modulators and non-substrates) and second to identify the binding sites. After thorough statistical analysis, we conclude despite the various challenges that molecular docking should not be underestimated as differences between the distinct groups were significant. However, when it comes to defining the binding site, care must be taken, since consensus throughout literature could not be reached.

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Acknowledgement

There is no conflict of interest. We are grateful to the German Academic Exchange Service (DAAD) and the National Research Institute, Sudan for stipends to M.Z. and M.E.M. S., respectively, as well as to the Johannes University, Mainz for an intramural PhD position to O.K.

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Authors and Affiliations

  1. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Rhineland-Palatinate, Germany

    Maen Zeino, Mohamed E. M. Saeed, Onat Kadioglu & Thomas Efferth

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  1. Maen Zeino
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  2. Mohamed E. M. Saeed
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  3. Onat Kadioglu
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  4. Thomas Efferth
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Correspondence to Thomas Efferth.

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Zeino, M., Saeed, M.E.M., Kadioglu, O. et al. The ability of molecular docking to unravel the controversy and challenges related to P-glycoprotein—a well-known, yet poorly understood drug transporter. Invest New Drugs 32, 618–625 (2014). https://doi.org/10.1007/s10637-014-0098-1

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