title: Predictive power of molecular dynamics receptor structures in virtual screening.
abstract: Molecular dynamics (MD) simulation is a well-established method for understanding protein dynamics. Conformations from unrestrained MD simulations have yet to be assessed for blind virtual screening (VS) by docking. This study presents a critical analysis of the predictive power of MD snapshots to this regard, evaluating two well-characterized systems of varying flexibility in ligand-bound and unbound configurations. Results from such VS predictions are discussed with respect to experimentally determined structures. In all cases, MD simulations provide snapshots that improve VS predictive power over known crystal structures, possibly due to sampling more relevant receptor conformations. Additionally, MD can move conformations previously not amenable to docking into the predictive range.
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093-0365, United States. senichols@ucsd.edu
authors.forename: Sara E
authors.initials: SE
authors.lastname: Nichols
authors.forename: Riccardo
authors.initials: R
authors.lastname: Baron
authors.forename: Anthony
authors.initials: A
authors.lastname: Ivetac
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D003578:Cytochrome-c Peroxidase / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012372:ROC Curve; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D014584:User-Computer Interface
chemical_list: D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D003578:Cytochrome-c Peroxidase; D054303:HIV Reverse Transcriptase