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.