Modeling Protein–Protein Recognition in Solution Using the Coarse-Grained Force Field SCORPION

We present here the SCORPIONSolvated COaRse-grained Protein interactIONforce field, a physics-based simplified coarse-grained (CG) force field. It combines our previous CG protein model and a novel particle-based water model which makes it suitable for Molecular Dynamics (MD) simulations of protein association processes. The protein model in SCORPION represents each amino acid with one to three beads, for which electrostatic and van der Waals effective interactions are fitted separately to reproduce those of the all-atom AMBER force field. The protein internal flexibility is accounted for by an elastic network model (ENM). We now include in SCORPION a new Polarizable Coarse-Grained Solvent (PCGS) model, which is computationally efficient, consistent with the protein CG representation, and yields accurate electrostatic free energies of proteins. SCORPION is used here for the first time to perform hundreds-of-nanoseconds-long MD simulations of protein/protein recognition in water, here the case of the barnase/barstar complex. These MD simulations showed that, for five of a total of seven simulations starting from several initial conformations, and after a time going from 1 to 500 ns, the proteins bind in a conformation very close to the native bound structure and remain stable in this conformation for the rest of the simulation. An energetic analysis of these MD show that this recognition is driven both by van der Waals and electrostatic interactions between proteins. SCORPION appears therefore as a useful tool to study protein–protein recognition in a solvated environment