Monte Carlo refinement of rigid-body protein docking structures with backbone displacement and side-chain optimization

Structures of hitherto unknown protein complexes can be predicted by docking the solved protein monomers. Here, we present a method to refine initial docking estimates of protein complex structures by a Monte Carlo approach including rigid-body moves and side-chain optimization. The energy function used is comprised of van der Waals, Coulomb, and atomic contact energy terms. During the simulation, we gradually shift from a novel smoothed van der Waals potential, which prevents trapping in local energy minima, to the standard Lennard-Jones potential. Following the simulation, the conformations are clustered to obtain the final predictions. Using only the first 100 decoys generated by a fast Fourier transform (FFT)-based rigid-body docking method, our refinement procedure is able to generate near-native structures (interface RMSD <2.5 angstrom) as first model in 14 of 59 cases in a benchmark set. In most cases, clear binding funnels around the native structure can be observed. The results show the potential of Monte Carlo refinement methods and emphasize their applicability for protein-protein docking.