I-ATTRACT: a New Flexible Docking Approach for Investigating Protein Protein Interactions

Abstract

Many of the most important processes in the cell are carried out by large molecular machines built up from multiple proteins. However, structural data for a large fraction of known and putative complexes is still lacking. Computational docking methods aim at predicting protein complexes based on the structure of the individual constituents. A new protein-protein docking approach, i-ATTRACT has been evaluated on a large benchmark. The docking combines rigid body degrees of freedom and fully flexible interface residues in a simultaneous potential energy minimization. To our knowledge this is the first docking method performing an energy minimization in degrees of freedom of multiple scale. Procedures combining Monte Carlo sampling and energy minimization were applied as well. Refinement of rigid body docking solutions from a systematic search with unbound protein structures using ATTRACT [1] shows promising results on a large number of cases. i-ATTRACT is able to significantly improve results for initial structural deviations of up to 8 A from bound geometries. Compared to molecular dynamics this refinement procedure comes at low computational cost but shows more efficient sampling by combining small-scale conformational rearrangements and large-scale center-of-mass displacements.Reference:[1] de Vries, S., Zacharias, M. (2012), ATTRACT-EM: A New Method for the Computational Assembly of Large Molecular Machines Using Cryo-EM Maps. PLOS ONE 7(12): e49733. doi:10.1371/journal.pone.0049733.