MOLECULAR-DYNAMICS OF ACETYLCHOLINESTERASE DIMER COMPLEXED WITH TACRINE

We have studied the dynamic properties of acetylcholinesterase dimer f rom Torpedo californica liganded with tacrine (AChE-THA) in solution u sing molecular dynamics. The simulation reveals fluctuations in the wi dth of the primary channel to the active site that are large enough to admit substrates. Alternative entries to the active site through the side walls of the gorge have been detected in a number of structures. This suggests that transport of solvent molecules participating in cat alysis can occur across the porous wall, contributing to the efficienc y of the enzyme.