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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.

SUBMITTER: Nichols SE

PROVIDER: S-EPMC3124922 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Predictive power of molecular dynamics receptor structures in virtual screening.

Nichols Sara E SE Baron Riccardo R Ivetac Anthony A McCammon J Andrew JA

Journal of chemical information and modeling 20110512 6

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 d ...[more]

PMID: 21534609

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