A grand challenge in biophysics has been the characterization of complete protein-protein binding pathways at atomic resolution. We have applied the weighted ensemble strategy to enable the atomistic simulation of 203 fully continuous binding pathways in explicit solvent for the proteins, barnase and barstar, yielding a computed k<sub>on </sub>that is within error of experiment. The simulation was completed within a month using 1600 CPU cores at a time, demonstrating that such simulations of multi-microsecond protein-protein binding processes are now practical on typical resources, particularly using the latest GPU-accelerated computing. I will present insights about the binding mechanism from our simulation and remaining challenges in generating binding pathways and rate constants.

Protein-protein binding pathways and calculations of rate constants using fully continuous explicit solvent simulations

2019 Spring National Meeting

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