Rosetta-MPDock: A Novel Computational Tool for Protein-Protein Docking within the Membrane Bilayer

Abstract

Even though over 50% of drugs target membrane proteins, that are encoded by ∼30% of the genome, as little as 1-2% of the structures in the ProteinDataBank belong to them. This discrepancy arises due to major challenges in over-expression, purification, reconstitution into membrane mimetics, and structure determination by various methods. Not surprisingly, interactions between membrane proteins that occur inside the membrane bilayer are even more difficult to study. Here we present a novel method, RosettaMPDock, to predict protein-protein interactions within the membrane. The tool was developed inside the Rosetta software suite, the leading software for biomolecular structure prediction, docking, and design. RosettaMPDock builds upon a new framework for modeling membrane proteins in Rosetta. This framework follows newest standards for object-oriented design and integrates smoothly into Rosetta3's architecture. It further greatly facilitates the development of new protocols such as RosettaMPDock.