The entire reaction takes less than 2 milliseconds, an astounding speed for a biological enzyme, but one obviously necessary and optimized by aeons of evolution to allow rapid fight or flight by organisms. The crystal structure of the AChE enzyme was solved a few years ago in the laboratory of Joel Sussman and Israel Silman of the Weizmann Institute in Rehovot, Israel. The active site of the molecule appeared to be in a channel much too narrow to process acetylcholine and expel the products rapidly. What they discovered was that the atomic motion of AChE can widen the main channel to the active site, and even open extra channels to permit acetylcholine to enter and be broken down by the enzyme. This steering speeds the reaction by a factor of ten.
Computation is essential in our research.
We used the resources of all four NSF computational laboratories, at San Diego, Pittsburgh, the University of Illinois, and Cornell, in our own work. We are now using the massively parallel Intel Paragon machine at San Diego, which has 400 processors, to continue our work, as well as the Cray C90 machine, also at San Diego, and a group of Silicon Graphics machines at Illinois. McCammon's work is supported by grants from the National Science Foundation and the National Institutes of Health. McCammon joined UCSD earlier this year from the University of Houston, where he was the M.D. Anderson Professor of Chemistry and director of the Institute for Molecular Design. The tighter the binding, the more effective the drug is likely to be.