Interactive Docking Workshop: Docking the Anticancer Drug Belinostat to Its Cellular Histone Deacetylase (HDAC) Target

DockIT is an interactive molecular docking tool suitable for teaching students about concepts related to drug–receptor interaction. Its most unique feature is the ability to model both local and global conformational change in the receptor based on information derived from the trajectory of a molecular dynamics (MD) simulation. The workshop presented here uses DockIT to bind the anticancer drug belinostat to its target protein, histone deacetylase 6 (HDAC6). To model the conformational response of HDAC6 to the binding of belinostat, a 200 ns explicit-solvent MD simulation was performed on HDAC6. The workshop challenges students to predict the experimentally determined binding pose of belinostat by finding a minimum of the binding energy. The task is “semi-blind” in the sense that the binding pocket location on HDAC6 is indicated, but not belinostat’s orientation. The workshop contrasts with previous docking workshops that use automated docking tools in that the docking process itself is under the control of the student, enabling them to experiment and test ideas. Results of a pre- and postworkshop multiple choice questionnaire showed an improvement in the students’ understanding of key features of molecular binding.