Additionally, the OpenMM SEEKR2 plugin enables us to evaluate milestone crossings at every timestep while incurring little extra computational cost (as opposed to a default of milestone crossing evaluation every 10 timesteps when using NAMD). Compared to a conventional OpenMM simulation (without SEEKR2), only a ~25% loss of speed was observed for these systems when the milestoning protocols were included in the SEEKR2 plugin.