title: Homology modeling and binding site assessment of the human P-glycoprotein.
abstract: BACKGROUND
  Due to its impact on multidrug resistance and pharmacokinetics P-glycoprotein (P-gp) has been identified as an important anti-target in pharmaceutical research. Recent publication of the mouse P-gp structure prompted us to build a new model for human P-gp and investigate its binding-site characteristics.
  
  
  RESULTS
  We developed and validated the human P-gp model that was used for induced-fit docking of experimentally characterized P-gp substrates. Residues located in the binding pocket are in good correlation with the results of side-directed mutagenesis studies. However, enrichment studies aimed at discriminating inhibitors and substrates from decoys resulted in only limited enrichments.
  
  
  CONCLUSIONS
  A mouse P-gp-based homology model might be useful when analyzing protein-ligand interactions of known human P-gp substrates if induced-fit effects are considered.
authors: Discovery Chemistry, Gedeon Richter, PO Box 27, H-1475 Budapest, Hungary.
authors: Akos
authors: A
authors: Tarcsay
authors: György M
authors: GM
authors: Keseru
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D018432:Drug Resistance, Multiple; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004364:Pharmaceutical Preparations