Structural Bioinformatics FRODOCK: a new approach for fast rotational protein-protein docking

Motivation: Prediction of protein-protein complexes from the coor-dinates of their unbound components usually starts by generating many potential predictions from a rigid-body six-dimensional search followed by a second stage that aims to refine such predictions. Here, we present and evaluate a new method to effectively address the complexity and sampling requirements of the initial exhaustive search. In this approach we combine the projection of the interaction terms into 3D grid-based potentials with the efficiency of spherical harmonics approximations to accelerate the search. The binding energy upon complex formation is approximated as a correlation function composed of van der Waals, electrostatics and desolvation potential terms. The interaction energy minima are identified by a novel, fast and exhaustive rotational docking search combined with a simple translational scanning. Results obtained on standard pro-tein-protein benchmarks demonstrate its general applicability and robustness. The accuracy is comparable to that of existing state-of-the-art initial exhaustive rigid-body docking tools, but achieving su-perior efficiency. Moreover, a parallel version of the method per-forms the docking search in just a few minutes, openning new appli-cation opportunities in the current “omics ” world