Crystal contacts as nature's docking solutions

Evgeny Krissinel
2010 Journal of Computational Chemistry  
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
more » ... tatively 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. where m(X), J k (X), and γ (X) stand for the mass, kth principal moment of inertia, and symmetry number of molecule X,
doi:10.1002/jcc.21303 pmid:19421996 fatcat:yyancya3ozax3db6cv2mecx5xy