ICM-DISCO docking by global energy optimization with fully flexible side-chains.
The ICM-DISCO (Docking and Interface Side-Chain Optimization) protein-protein-docking method is a direct stochastic global energy optimization from multiple starting positions of the ligand. The first step is performed by docking of a rigid all-atom ligand molecule to a set of soft receptor potentials precalculated on a 0.5 A grid from realistic solvent-corrected force-field energies. This step finds the correct solution as the lowest energy conformation in almost 100% of the cases in which interfaces do not change on binding. The second step is needed to deal with the induced changes and includes the global optimization of the interface side-chains of up to 400 best solutions. The CAPRI predictions were performed fully automatically with this method. Available experimental information was included as a filtering step to favor expected docking surfaces. In three of the seven proposed targets, the ICM-DISCO method found a good solution (>50% of correct contacts) within the five submitted models. The procedure is global and fully automated. We demonstrate that the algorithm handles the induced changes of surface side-chains but is less successful if the backbone undergoes large-scale rearrangements.
Fernández-Recio
Juan
J
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Totrov
Maxim
M
Abagyan
Ruben
R
D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000956:Antigens, Viral; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology; D005098:Exotoxins / Q000737:chemistry / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009010:Monte Carlo Method; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry / Q000378:metabolism; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000378:metabolism; D000516:alpha-Amylases / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D000906:Antibodies; D000956:Antigens, Viral; D001426:Bacterial Proteins; D036022:Capsid Proteins; D005098:Exotoxins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C117980:SpeA protein, Streptococcus pyogenes; C061332:VP6 protein, Rotavirus; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr; C110847:HPr kinase; D017346:Protein Serine-Threonine Kinases; D000516:alpha-Amylases