Title: Induced-fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design Xu Y, Colletier JP, Jiang H, Silman I, Sussman JL, Weik M Ref: Protein Science, 17:601, 2008 : PubMed
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.
        
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Xu Y, Colletier JP, Jiang H, Silman I, Sussman JL, Weik M (2008) Induced-fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design Protein Science17: 601-5
Xu Y, Colletier JP, Jiang H, Silman I, Sussman JL, Weik M (2008) Protein Science17: 601-5