In summary, SEEKR2 performs MMVT and conventional milestoning simulations with an extensible interface for milestone/Voronoi cell definitions, and performs the simulations using either a CPU platform, or, much more quickly and efficiently, using the GPU platform. Only *12 results using one-dimensional concentric spherical milestone shapes have been used for this study, but more dimensions and other milestone shapes have been implemented, and will be straightforward to attempt. We've shown that SEEKR2, in general, performs better than earlier versions of SEEKR to recreate the kinetics and thermodynamics for two benchmark systems and has performed well on a new, challenging system with a complex ligand and slow unbinding kinetics. The new HMR feature allows for even faster calculations while still giving correct results. SEEKR2 contains many of the utilities that members of the biophysics community may find useful for their own milestoning calculations.