Oliver Hucke, René Coulombe, Pierre Bonneau, Mégan Bertrand-Laperle, Christian Brochu, James Gillard, Marc-André Joly, Serge Landry, Olivier Lepage, Montse Llinàs-Brunet, Marc Pesant, Martin Poirier, Maude Poirier, Ginette McKercher, Martin Marquis, George Kukolj, Pierre L Beaulieu, Timothy A Stammers
The design and preliminary SAR of a new series of 1H-quinazolin-4-one (QAZ) allosteric HCV NS5B thumb pocket 2 (TP-2) inhibitors was recently reported. To support optimization efforts, a molecular dynamics (MD) based modeling workflow was implemented, providing information on QAZ binding interactions with NS5B. This approach predicted a small but critical ligand-binding induced movement of a protein backbone region which increases the pocket size and improves access to the backbone carbonyl groups of Val 494 and Pro 495...
March 13, 2014: Journal of Medicinal Chemistry