Title : Development of Chemical and Biological Therapeutics against Chemical Warfare Poisoning: Butyrylcholinesterase and Paraoxonase-1

Abstract :

Chemical warfare agents, in particular, organophosphorus (OP) compounds continue to pose severe threats to civilian and military personnel as there are no known permanent treatments available that works against all of the OP compounds. Recent usages of such weapons of mass destruction have raised the severity of this problem even further. This presentation will focus on computational and experimental efforts to design possible chemical and biochemical therapeutics against OP exposure. Efforts to utilize Butyrylcholinesterase (BuChE) as a drug against nerve agents will be summarized briefly. Computational insights into the rational engineering of Paraoxonase-1 (PON1) as a scavenger of OP compounds will also be discussed. In particular, the focus will be on developing a binding model, variant design at H115 and K192 positions to increase the efficiency, and possible operating mechanism of PON1. Furthermore, as the active site of PON1 is not known; thus, development of a photo-affinity label for labeling of PON1 by means of excited state calculations and time-resolved spectroscopic methods will be summarized.