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Updated: Jun 3, 2026

Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
Homology modeling and binding site assessment of the human P-glycoprotein
Akos Tarcsay1, György M Keseru
1Discovery Chemistry, Gedeon Richter, PO Box 27, H-1475 Budapest, Hungary.
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.
Conclusion:
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.
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