User:Yuan-Ping Pang/Sandbox 1

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

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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 potential antidotes to antagonize the extracellular or intracellular BoNTA [refs]. HAB (to be published) is one such inhibitor that exhibits nanomolar potency in inhibiting BoNTAe and has a functional group coordinating the zinc divalent cation embedded in the active site of BoNTAe according to the simulations using the cationic dummy atom approach [refs]. Multiple molecular dynamics simulations of HAB•BoNTAe (20 10-ns-long simulations) suggest that one functional group is highly flexible or intrinsically disordered; the percentages of the top three most-populated conformations of the complex (Models 1-3) are 20.8%, 13.4% and 11.9%, respectively. To evaluate the computational methods, the coordinates of the three models are released before the forthcoming crystal structure of HAB•BoNTAe. Only 33% of the heavy atoms of HAB are released in the models below. The full structure of HAB will be released upon manuscript acceptance.

Download the coordinates of Model1 (PDB format)

Download the coordinates of Model2 (PDB format)

Download the coordinates of Model3 (PDB format)

References & Notes