User:Yuan-Ping Pang/Sandbox 1

From Proteopedia

Model: Botulinum Neurotoxin Serotype A Endopeptidase Liganded with a Nanomolar Small-Molecule Inhibitor HAB - by YP Pang

Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are sought in our laboratories as antidotes to antagonize the extracellular or intracellular toxin [refs]. HAB is one such inhibitor that exhibits nanomolar potency in inhibiting BoNTAe (to be published). Multiple molecular dynamics simulations of HAB•BoNTAe (20 10-ns-long simulations) suggest that one functional group is highly flexible; the percentages of the top three most-populated conformations of the complex (models 1-3) are 20.8%, 13.4% and 11.9%, respectively. The coordinates of the three models are released before the forthcoming crystal structure of HAB•BoNTAe. Only 60% of the heavy atoms of HAB are released in the models below. The full structure of HAB will be released upon manuscript acceptance.