Benchmarking simulations were performed on a Linux machine with an NVIDIA Quadro RTX 5000 GPU with 16 GB RAM and an Intel Xeon W-10885M CPU. SEEKR2 milestoning simulations were run using the OpenMM version 7.7 for all the seven host-guest complexes and the trypsin benzamidine complexes, using 1 GPU with CUDA version 10. . Benchmarking rates for SEEKR2 simulations performed on the seven host-guest complexes and the trypsin-benzamidine complex performed on a single NVIDIA Quadro RTX 5000 GPU.