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Crystal contacts as nature's docking solutions
Author(s) -
Krissinel Evgeny
Publication year - 2009
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.21303
Subject(s) - misrepresentation , docking (animal) , crystal (programming language) , protein data bank (rcsb pdb) , crystal structure , chemistry , statistical physics , macromolecule , computational chemistry , crystallography , physics , thermodynamics , computer science , stereochemistry , medicine , biochemistry , nursing , political science , law , programming language
The assumption that crystal contacts reflect natural macromolecular interactions makes a basis for many studies in structural biology. However, the crystal state may correspond to a global minimum of free energy where biologically relevant interactions are sacrificed in favor to unspecific contacts. A large‐scale docking experiment was performed to assess the extent of misrepresentation of natural (in‐solvent) protein dimers by crystal packing. As found, the failure rate of docking may be quantitatively interpreted if both calculation errors and misrepresentation effects are taken into account. The failure rate analysis is based on the assumption that crystal structures reflect thermodynamic equilibrium between different dimeric configurations. The analysis gives an estimate of misrepresentation probability, which suggests that weakly bound complexes with K D ≥ 100 μM (some 20% of all dimers in the PDB) have higher than 50% chances to be misrepresented by crystals. The developed theoretical framework is applicable in other studies, where experimental results may be viewed as snapshots of systems in thermodynamic equilibrium. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010