title: On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data.
abstract: There are several indications that a given compound or a set of related compounds can bind in different modes to a specific binding site of a protein. This is especially evident from X-ray crystallographic structures of ligand-protein complexes. The availability of multiple binding modes of a ligand in a binding site may present an advantage in drug design when simultaneously optimizing several criteria. In the case of the design of anti-HIV compounds we observed that the more active compounds that are also resilient against mutation of the non-nucleoside binding site of HIV1-reverse transcriptase make use of more binding modes than the less active and resilient compounds.
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003460:Crystallization; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D008024:Ligands; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase