Zeino Maen, Saeed Mohamed E M, Kadioglu Onat, Efferth Thomas
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Rhineland-Palatinate, Germany.
Invest New Drugs. 2014 Aug;32(4):618-25. doi: 10.1007/s10637-014-0098-1. Epub 2014 Apr 22.
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.
P-糖蛋白是与肿瘤耐药性相关的最关键的膜转运蛋白。人们付出了巨大努力来阐明其复杂的转运机制并鉴定该转运蛋白的调节剂。然而，底物和调节剂之间的界限非常模糊，且鉴定P-糖蛋白内的结合位点很复杂。在此，我们对这些问题进行深入综述，并使用分子对接来评估其能力：第一，区分三组（底物、调节剂和非底物）；第二，鉴定结合位点。经过全面的统计分析，我们得出结论，尽管存在各种挑战，但分子对接不应被低估，因为不同组之间的差异很显著。然而，在定义结合位点时必须谨慎，因为整个文献中未能达成共识。
