Benchmarking was performed to compare the performance of SEEKR2 against the original MMVT-SEEKR implementation in NAMD and a conventional OpenMM simulation of the same molecular system. Comparisons are listed in Table . For the trypsin-benzamidine system, the *7 SEEKR2 OpenMM implementation performs almost 20 times faster than the NAMD-based MMVT-SEEKR code running on a GPU, which were re-run for the purposes of this study, and almost six times faster than the old MMVT-SEEKR running on a 68-core CPU node. The differences between the performances of the newer OpenMM approach, and the use of NAMD for the MD portion of the SEEKR2 calculations, are primarily caused by the implementation of CUDA code to perform the milestoning procedure directly in an OpenMM plugin. In constrast, the NAMD approach currently utilizes a TCL-based interace, which negatively impacts the speed of milestoning calculations, even when the milestone crossings are only monitored every 10 timesteps. The NAMD3 program can run MD simulations on GPUs very efficiently, on-par with the speed of OpenMM on GPUs. However, at the time of this writing, NAMD3 has not implemented the TCL interface required to run milestoning, so we are currently limited to NAMD2, which, as can be seen from Table , does not run as efficiently on GPUs as OpenMM.