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Improving CAPRI predictions: optimized desolvation for rigid-body docking.

Juan Fernández-Recio·Ruben Abagyan·Maxim Totrov
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Abstract

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.

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AlgorithmsAnimalsBacterial ProteinsBinding SitesComputational BiologyComputer SimulationCrystallography, X-RayDatabases, ProteinDimerizationInternetMacromolecular SubstancesModels, MolecularModels, StatisticalMolecular ConformationProtein BindingProtein ConformationProtein FoldingProtein Interaction MappingProtein Structure, TertiaryProteomicsReproducibility of ResultsSequence AlignmentSoftwareStatic ElectricityStructural Homology, ProteinJournal ArticleResearch Support, Non-U.S. Gov't

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Juan Fernández-Recio, Ruben Abagyan, Maxim Totrov. 2005-08-01. Improving CAPRI predictions: optimized desolvation for rigid-body docking.. https://doi.org/10.1002/prot.20575

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