Empirical entropic contributions in computational docking: evaluation in APS reductase complexes

J Comput Chem. 2008 Aug;29(11):1753-61. doi: 10.1002/jcc.20936.


The results from reiterated docking experiments may be used to evaluate an empirical vibrational entropy of binding in ligand-protein complexes. We have tested several methods for evaluating the vibrational contribution to binding of 22 nucleotide analogues to the enzyme APS reductase. These include two cluster size methods that measure the probability of finding a particular conformation, a method that estimates the extent of the local energetic well by looking at the scatter of conformations within clustered results, and an RMSD-based method that uses the overall scatter and clustering of all conformations. We have also directly characterized the local energy landscape by randomly sampling around docked conformations. The simple cluster size method shows the best performance, improving the identification of correct conformations in multiple docking experiments.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Carbohydrates / chemistry
  • Cluster Analysis
  • Empirical Research
  • Entropy*
  • Ligands
  • Oxidoreductases Acting on Sulfur Group Donors / chemistry
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism*
  • Protein Binding
  • Protein Conformation


  • Carbohydrates
  • Ligands
  • Oxidoreductases Acting on Sulfur Group Donors
  • adenylylsulfate reductase