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Empirical entropic contributions in computational docking: Evaluation in APS reductase complexes
Author(s) -
Chang Max W.,
Belew Richard K.,
Carroll Kate S.,
Olson Arthur J.,
Goodsell David S.
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20936
Subject(s) - docking (animal) , entropy (arrow of time) , chemistry , cluster analysis , energy landscape , computational chemistry , cluster (spacecraft) , statistical physics , biological system , computer science , physics , thermodynamics , machine learning , biology , biochemistry , medicine , nursing , programming language
Abstract 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. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008