Protein domain movement involved in binding of belinostat and HPOB as inhibitors of histone deacetylase 6 (HDAC6): a hybrid automated-interactive docking study.

ABSTRACT: DockIT is a tool for interactive molecular docking that can model both the local and global conformational response of the receptor to the docking of a ligand based on information from a molecular dynamics simulation. Using DockIT we have investigated the binding process of two histone deacetylase (HDAC) inhibitors to HDAC6: the nonselective approved drug belinostat and the preclinical HPOB. To model HDAC6's conformational response to the binding of the inhibitors we performed a 200-nanosecond explicit-solvent molecular dynamics simulation on HDAC6. Unexpectedly the simulation revealed a domain movement that affects the size and shape of the binding pocket. Using automated docking and a rigid model for the inhibitors, the domain movement continuously adapts the pocket to the presence of th

SUBMITTER: Iakovou G 

PROVIDER: S-EPMC12263812 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature