The simulation box was built using tleap, also a part of the Amber 16 package. We used the protein and ligand force field parameters from the Amberff14sb 32 and GAFF 1.8 33 force field respectively. Each protein-ligand complex was solvated using TIP3P waters 34 in a cubic box with 10 Å padding. Two Na+ ions and four Cl-ions were added to neutralize the JNK1 and CDK2 protein-ligand complexes respectively. 3.2. Equilibration and production MD simulation details. The MD simulations were performed using OpenMM 7.1.1 . We used a Langevin integrator with 2 fs time step and a friction coefficient of 1 ps -1 . A cutoff of 10 Å was used for real-space electrostatics and Lennard-Jones forces, while long-range electro-statics was calculated using the particle mesh Ewald method.