Interpreting the effect of methyl group at the three carbon bridge of (-)-huperzine A on its anticholinesterase activity by molecular dynamics method

Based on the recently resolved crystal structure of complex (-)-huperzine A-AChE, we simulated the interaction between (-)-huperzine A analogues and AChE using molecular dynamics method. It was revealed that the methyl group at the three carbon bridge of (-)-huperzine A can form a weak hydrogen bond with the phenol hydroxyl oxygen of Tyr121 and the main-chain oxygen of Gly118 of AChE, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.