title: Adaptive BP-Dock: An Induced Fit Docking Approach for Full Receptor Flexibility.
abstract: We present an induced fit docking approach called Adaptive BP-Dock that integrates perturbation response scanning (PRS) with the flexible docking protocol of RosettaLigand in an adaptive manner. We first perturb the binding pocket residues of a receptor and obtain a new conformation based on the residue response fluctuation profile using PRS. Next, we dock a ligand to this new conformation by RosettaLigand, where we repeat these steps for several iterations. We test this approach on several protein test sets including difficult unbound docking cases such as HIV-1 reverse transcriptase and HIV-1 protease. Adaptive BP-Dock results show better correlation with experimental binding affinities compared to other docking protocols. Overall, the results imply that Adaptive BP-Dock can easily capture binding induced conformational changes by simultaneous sampling of protein and ligand conformations. This can provide faster and efficient docking of novel targets for rational drug design.
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287, United States.
authors.forename: Ashini
authors.initials: A
authors.lastname: Bolia
authors.affiliation: Department of Physics, Center for Biological Physics, Arizona State University , Tempe, Arizona 85287, United States.
authors.forename: S Banu
authors.initials: SB
authors.lastname: Ozkan
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation / Q000379:methods*; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D004798:Enzymes; D011134:Polysaccharides; C107733:cyanovirin N