To execute SEEKR2 simulations, users must have access to a Linux-based machine. Simulations can be carried out with just one processor, though this will be very slow for systems of interest in biomedical research and drug discovery. A GPU device or cluster is recommended for optimal performance of MD engines. When working with large receptor-ligand complexes, faster processors and greater memory capacity may be required to implement SEEKR2 calculations successfully. Users are advised to run the simulations while monitoring the resource usage to estimate the necessary storage and memory. Employing multiple processors for SEEKR2 simulations within each anchor is recommended for BD simulations, where multiple processors can be utilized. When the NAMD simulation engine is used, employing multiple CPU processors will also accelerate the calculations. However, when using OpenMM, increasing the number of CPU processors may not lead to faster simulation speeds.