Predicting protein interaction sites: binding hot-spots in protein-protein and protein-ligand interfaces.
BACKGROUND
Protein assemblies are currently poorly represented in structural databases and their structural elucidation is a key goal in biology. Here we analyse clefts in protein surfaces, likely to correspond to binding 'hot-spots', and rank them according to sequence conservation and simple measures of physical properties including hydrophobicity, desolvation, electrostatic and van der Waals potentials, to predict which are involved in binding in the native complex.


RESULTS
The resulting differences between predicting binding-sites at protein-protein and protein-ligand interfaces are striking. There is a high level of prediction accuracy (< or =93%) for protein-ligand interactions, based on the following attributes: van der Waals potential, electrostatic potential, desolvation and surface conservation. Generally, the prediction accuracy for protein-protein interactions is lower, with the exception of enzymes. Our results show that the ease of cleft desolvation is strongly predictive of interfaces and strongly maintained across all classes of protein-binding interface.
Burgoyne
Nicholas J
NJ
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Jackson
Richard M
RM
D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D005189:False Positive Reactions; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D012984:Software; D055672:Static Electricity
D008024:Ligands; D011506:Proteins