Investigation of the binding mode of (−)-meptazinol and bis-meptazinol derivatives on acetylcholinesterase using a molecular docking method

Abstract

Molecular docking has been performed to investigate the binding mode of (−)-meptazinol (MEP) with acetylcholinesterase (AChE) and to screen bis-meptazinol (bis-MEP) derivatives for preferable synthetic candidates virtually. A reliable and practical docking method for investigation of AChE ligands was established by the comparison of two widely used docking programs, FlexX and GOLD. In our hands, we had more luck using GOLD than FlexX in reproducing the experimental poses of known ligands (RMSDS,S) and (SR,RS) and with a 2- to 7-carbon linkage. Although there are still no biological results to confirm the predictive power of this method, the current study could provide an alternate tool for structural optimization of (−)-MEP as new AChE inhibitors. bem