Refining multimeric protein complexes using conservation, electrostatics and probabilistic selection

We introduce a multimeric docking refinement method that uses a scoring function based on a tight coupling between evolutionary conservation, geometry and pairwise interactions. Detection of protein complexes and their structures is crucial for understanding the role of protein complexes in the basic biology of organisms. Computational methods can provide researchers with a good starting point for the analysis of protein complexes. However, computational docking methods are often not accurate and their results need to be further refined to improve interface packing. Additionally, most docking methods focus on dimers due to the exponential growth in computational complexity caused by the addition of monomeric units. Multimeric docking and refinement methods should employ efficient selection criteria to reduce the search space. The incorporation of evolutionary conservation allows us to bias our results towards possible functional interface. We combine our search with a probabilistic selection scheme that allows us to escape local energy minima. Our results suggest that our refinement scheme can efficiently handle complexes with more than 2 monomers and help biasing the results towards complexes with native interactions, filtering out false positive results. We produce structures with better IRMSDs with respect to the known complexes and lower energies than those initial docked structures.