Abstract
Crystal structures of acetylcholinesterase complexed with ligands are compared with side-chain
conformations accessed by native acetylcholinesterase in molecular dynamics (MD) simulations.
Several crystallographic conformations of a key residue in a specific binding site are accessed in a
simulation of native acetylcholinesterase, although not seen in rotomer plots. Conformational changes
upon ligand binding thus involve preexisting equilibrium dynamics. Consequently, rational drug design
could benefit significantly from conformations monitored by MD simulations of native targets.