Ligand Binding to the Pregnane X Receptor by Geometric Matching of Hydrogen Bonds. Robert-Paul Berretty, David Hsu, Lutz Kettner, Ajith Mascarenhas, Matthew R. Redinbo, Jack Snoeyink, and Ryan Watkins. Poster in: The Sixth Annual International Conference on Research in Computational Molecular Biology (RECOMB), 2002.
Hydrogen bonds are important in protein-ligand interactions. We describe a geometric model of hydrogen bonds, which we use to study ligand binding to the Pregnane X Receptor (PXR). PXR binds drug ligands promiscuously. The recently determined structure of PXR in humans (hPXR) reveals that its binding pocket is large, smooth, and uniformly hydrophobic [], leading to the hypothesis that hydrogen bonds are the main determinant of binding conformations. Our objective in this work is to identify potential ligand binding conformations to PXR based on hydrogen bond geometry and use them as a starting point for ranking ligands in terms of the binding affinity to human and mouse versions of PXR.
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