Improving CAPRI predictions: optimized desolvation for rigid-body docking.
The ICM Docking and Interface Side-Chain Optimization (ICM-DISCO) showed promising predictive results during the first CAPRI experiment by successfully finding medium- or high-accuracy models in 3 of the 7 targets. A key factor was the ability to recognize near-native rigid-body geometries in a relatively low number of alternative docking poses, together with the successful refinement of the rigid-body docking interfaces. Since then, we have focused on improving the scoring function to optimally discriminate the near-native rigid-body conformations. For that, we have defined a new desolvation descriptor for rigid-body docking, based on atomic solvation parameters (ASPs) derived from octanol-water transfer experiments. This and other new approaches have been gradually incorporated into our docking procedure during our participation on the second CAPRI experiment. Overall, we produced reasonable models for 8 of the 9 official targets. Especially encouraging were those cases in which a homology model of 1 of the subunits had to be used during the docking simulations. And not less gratifying has been the successful prediction of antibody-antigen targets in a completely automatic, unrestrained fashion. In summary, our success rate (89%) shows a consistent improvement over the previous CAPRI rounds, and suggests that a correct desolvation description is key for improved protein-protein docking predictions.
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Juan
J
Fernández-Recio
Ruben
R
Abagyan
Maxim
M
Totrov
D000465:Algorithms; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D019281:Dimerization; D020407:Internet; D046911:Macromolecular Substances; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D016415:Sequence Alignment; D012984:Software; D055672:Static Electricity; D040681:Structural Homology, Protein
D001426:Bacterial Proteins; D046911:Macromolecular Substances