• DJ-1;
  • binding free energy;
  • molecular dynamics;
  • MM-PB(GB)SA;
  • Fragment MO


The computationally evaluated binding free energies of DJ-1, a clue protein to Parkinson's disease, with three potential curative agents are presented and discussed. The simple docking analysis offered fair absolute agreements of the calculated and the experimental binding energies while it failed to predict the binding affinity rank among the candidates. Computationally demanding analysis based on molecular dynamics and quantum chemical calculations unexpectedly worsen the gap between theory and experiment. The failure presumably comes from the inaccurate enthalpy terms owing to the basis set quality limitation and dispersion energy uncertainties, as well as from the inaccuracies of the entropy terms. The interfragment interaction analysis elucidated the driving force of the receptor–ligand affinity, which is not driven by Cys106 (the active site) but by the surrounding residues. © 2012 Wiley Periodicals, Inc.