Receptor-dependent (RD) 3D-QSAR approach of a series of benzylpiperidine inhibitors of human acetylcholinesterase (HuAChE)

► Receptor-dependent 3D-QSAR models of acetylcholinesterase benzylpiperidine inhibitors. ► Steric/electrostatic interaction energies are the RD-3D-QSAR independent variables. ► Steric term is more important than electrostatic in the human AChE-ligand complexes. ► Aromatic gorge (Tyr341, Trp439) and catalytic triad (His447) residues were selected. ► Potency prediction for E2020 (donepezil, R-enantiomer) and new designed ligands.