PyDockCG: New Coarse-Grained Potential for Protein–Protein Docking

Abstract

Protein-protein interactions are fundamental for the majority of biological processes, so their structural, functional, and energetic characterization is of enormous biotechnological and therapeutic interest. In recent years, a variety of computational docking approaches to the structural prediction of protein-protein complexes have been reported, with encouraging results. However, a major bottleneck is found in cases with conformational movements upon binding, for which docking algorithms have to be extended beyond the rigid-body framework by introducing flexibility. Given the high computational cost of flexible docking, coarse-grained models offer an efficient alternative to full-atom descriptions. This work describes pyDockCG, a new coarse-grained potential for protein-protein docking scoring and refinement, based on the known UNRES model for polypeptide chains. The main novelty is the inclusion of two new terms accounting for the Coulomb electrostatics and the solvation energy. The latter has been devised by adapting the EEF1 model to the coarse-grained approach, with optimal parameters for protein-protein docking. The coarse-grained potential yielded highly similar values to the full-atom scoring function pyDock when applied to the rigid body docking sets, but at much lower computational cost. This efficiency makes it suitable for the treatment of flexibility during docking.