The three-dimensional structures of MAPK1 were sourced from the Protein Data Bank under the accession code 2Y9Q, characterized by a Resolution of 1.55 Å and an R-Value Free of 0.177. Initial complex structures resulted from Docking simulations using Vina , establishing the binding pose for subsequent investigation via Umbrella Sampling. The setup of the simulation system was facilitated by the CHARMM-GUI web-based graphical interface . A cubic water box with an edge distance of 13 Å encapsulated the system, supplemented by a 0.15 M ionic NaCl solution for solvation neutralization. Gromacs software version 2021 , operationalized on the Dutch supercomputer Snellius, facilitated all simulations. The energy minimization of solvated systems involved a sequence of steps utilizing the steepest descent method and the conjugate gradient algorithm. Subsequently, equilibration occurred through 5 ns NPT (constant Number of atoms, Pressure, Temperature) ensemble after the first 1 ns NVT (constant Number of atoms, Volume, Temperature) ensemble.