Abstract
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.
Copyright 2003 Wiley-Liss, Inc.
MeSH terms
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Algorithms*
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Amino Acids / chemistry
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Antibodies / chemistry
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Antibodies / immunology
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Antigens, Viral*
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism
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Binding Sites
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Capsid Proteins / chemistry
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Capsid Proteins / immunology
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Exotoxins / chemistry
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Exotoxins / metabolism
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Hemagglutinin Glycoproteins, Influenza Virus / chemistry
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Macromolecular Substances
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism
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Models, Molecular*
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Monte Carlo Method
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Phosphoenolpyruvate Sugar Phosphotransferase System / chemistry
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Phosphoenolpyruvate Sugar Phosphotransferase System / metabolism
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Protein Interaction Mapping
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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Proteins / chemistry*
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Proteins / metabolism*
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Receptors, Antigen, T-Cell, alpha-beta / chemistry
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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alpha-Amylases / chemistry
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alpha-Amylases / metabolism
Substances
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Amino Acids
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Antibodies
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Antigens, Viral
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Bacterial Proteins
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Capsid Proteins
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Exotoxins
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Hemagglutinin Glycoproteins, Influenza Virus
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Macromolecular Substances
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Membrane Proteins
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Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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SpeA protein, Streptococcus pyogenes
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VP6 protein, Rotavirus
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Phosphoenolpyruvate Sugar Phosphotransferase System
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phosphocarrier protein HPr
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HPr kinase
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Protein Serine-Threonine Kinases
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alpha-Amylases