title: Molecular docking to flexible targets.
abstract: It is widely accepted that protein receptors exist as an ensemble of conformations in solution. How best to incorporate receptor flexibility into virtual screening protocols used for drug discovery remains a significant challenge. Here, stepwise methodologies are described to generate and select relevant protein conformations for virtual screening in the context of the relaxed complex scheme (RCS), to design small molecule libraries for docking, and to perform statistical analyses on the virtual screening results. Methods include equidistant spacing, RMSD-based clustering, and QR factorization protocols for ensemble generation and ROC analysis for ensemble selection.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, 3234 Urey Hall, MC-0340, San Diego, La Jolla, CA, 92093-0340, USA.
authors.forename: Jesper
authors.initials: J
authors.lastname: Sørensen
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Demir
authors.forename: Robert V
authors.initials: RV
authors.lastname: Swift
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Feher
authors.forename: Rommie E
authors.initials: RE
authors.lastname: Amaro
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000465:Algorithms; D019540:Area Under Curve; D019729:Carbon-Oxygen Ligases / Q000737:chemistry; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D024101:Mitochondrial Proteins / Q000737:chemistry; D062105:Molecular Docking Simulation / Q000379:methods*; D011336:Probability; D013816:Thermodynamics; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D019729:Carbon-Oxygen Ligases; C476580:REL1 RNA ligase, Trypanosoma brucei