Receptor Ensemble-Based Docking Methods

Working on a modified version of DOCK, a novel algorithm combining multiple flexible regions from experimental stmctures into a set of discrete receptor conformations was developed to incorporate flexibility into structure-based drug 

EC50 = 2.9 pM. To further structurally characterize the ligands mechanism of action, induced fit docking [51] was performed, showing evidence that five active flavonoids induce conformational change in the receptor upon binding. 

A series of N -benzyladenosine analogues were synthesized and evaluated for binding affinity on Toxoplasma gondii adenosine kinase, a relevant target for antitoxoplasma agents [67]. Among the tested analogues, N -(2,4-dimethoxybenzyl) adenosine displayed favorable antitoxoplasma activity (low micromolar) without 

Botulism, a neuroparalytic life-threatening disease, is caused by the botulinum neurotoxin serotype A (BoNTA). Although antibodies are effective in preventing the extracellular toxin to continue the intoxication process, they have no effect on prior intoxicated neurons. Targeting the BoNTA endopeptidase (BoNTAe) could be a valid alternative, since its inhibition may potentially neutralize the intracellular BoNTA. 

Pang et al. performed molecular dynamics (using AMBER) of a low micromolar inhibitor complexed with BoNTAe to guide lead optimization. They found a serotype-selective, small-molecule, high-nanomolar competitive inhibitor of BoNTAe, nearly an order of magnitude more potent than its parent compound [74]. This was also aided by a synthesis-based computer-aided molecular design protocol, which 

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