MODELING OF ACETYLCHOLINESTERASE

The enzyme responsible for the dehydration synthesis of acetylcholine(ACH), acetylcholinesterase(ACHE), is of particular interest in modern biophysics and biochemical research.

First, it is part of a very important biological function in animals - namely, nerve impulse. Residing in the postsynaptic gap, ACHE is responsible for deactivating ACH. When nerve impulses reach the end of the nerve, ACH is released into the cap. These molecules travel across the gap and then complex with a specific ion channel, facilitating the net flow of positive charge into the muscle, thus creating a voltage potentially resulting in the flex of the muscle. Once the ACH leaves the channel, it complexes with ACHE and is broken down into choline and acetic acid. The depletion of ACH in the synapse allows the muscle to relax. Our interest in this process has to do with the ion channel.

Second, our main biophysical interest in this enzyme has to do with its susceptibility to blockage. ACHE is the target of toxic military nerve agents such as sarin nerve gas. Our research in this aspect involves running computerized simulations of the enzymes as it complexes with those toxins. These simulations involve both molecular dynamic simulations using NWChem and quantum mechanical simulations of the active site with FIREBALL.