Ensemble docking in drug discovery or chemical biology uses dynamical simulations of target proteins to generate binding site conformations for docking campaigns. We show that 600 ns molecular dynamics simulations of four G-protein-coupled receptors in their membrane environments generate ensembles of protein configurations that, collectively, are selected by 70 99% of the known ligands of these proteins. Therefore, the process of ligand recognition by conformational selection can be reproduced by combining molecular dynamics and docking calculations. Clustering of the molecular dynamics trajectories, however, does not necessarily identify the protein conformations that are most often selected by the ligands.
|Number of pages||7|
|Journal||Journal of Physical Chemistry B|
|State||Published - Jun 27 2019|
Bibliographical noteFunding Information:
J.B. acknowledges the University of Alabama in Huntsville for support. J.B., J.C.S., and W.E.F. acknowledge support from the University of Tennessee, the LDRD program of ORNL, and SRE, the Cancer Research Informatics Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558).
© 2019 American Chemical Society.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Surfaces, Coatings and Films
- Materials Chemistry