The starting structure is obtained from the X-ray crystal structure of the JAK2-inhibitor complex domain with PDB ID: 3ZMM. Forcefield parameterization was done using the AMBER ff14SB forcefield with explicit solvation in a truncated octahedron 10 Å periodic box, 150 mM salt concentration, and a non-bonded cut-off radius of 9 Å. The solvated complex is slowly heated to 300 K followed by 20 ns each of NPT and NVT MD preparatory simulation, respectively carried at 300 K. All MD simulations have been carried out using the OpenMM simulation engine. SMD simulations were then performed where the COM of the inhibitor was restrained to 2.5 Å from the COM of the binding region of the receptor for 20 ns of constant pressure MD (NPT). Subsequently, the inhibitor was pulled by a moving harmonic restraint with a spring constant of 50000 kJ•mol-1•nm-2 in an SMD simulation from the 2.5 Å starting location to a final COM-COM distance of 16.0 Å over the course of 1000 ns of NVT MD. Eventually, concentric spherical Voronoi cells or "milestones" were defined at a distance of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 11.0, 12.0, 13.0, 14.0, 15.0, and 16.0 Å respectively from the COM of the binding site. MMVT simulations were then run using SEEKR for 400 ns per Voronoi cell.