title: Insights from comprehensive multiple receptor docking to HDAC8.
abstract: A systematic investigation of the available crystal structures of HDAC8 and of the influence of different receptor structures and docking protocols is presented. The study shows that the open conformation of HDAC8 may be preferred by ligands with flexible surface binding groups, as such a conformation allows the ligands to minimize their exposure to solvent upon binding. This observation allowed us to rationalize the excellent potency of pyrazole-based inhibitors compared to that of isoxazole-based inhibitors.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Brunsteiner
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Petukhov
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011720:Pyrazoles / Q000737:chemistry*; D012097:Repressor Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D056572:Histone Deacetylase Inhibitors; D007555:Isoxazoles; D011720:Pyrazoles; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases