Each ternary complex was solvated in an OPC water box with a length 12.5 nm from the protein edge in each dimension with 0.15 M NaCl using the program tleap from AmberTools22 . In total, 22 systems were prepared and underwent energy minimization, equilibration, and production phases with the Amber22 simulation package . Energy minimization of 70'000 steps was performed with position restraints with a force constant of 0.418 kJ/mol/nm 2 on the two proteins and the ligand (all atoms). Each minimized structure was equilibrated ten times with different randomly generated initial velocities to generate ten equilibrated structures. Each equilibration consisted of 75 ps NVT and 125 ps NpT simulations with gradually decreasing positional restraints (from 0.418 kJ/mol/nm 2 to 0.004 kJ/mol/nm 2 ) on proteins and ligands. An additional 1 ns NpT simulation was performed with a positional restraint of 0.004 kJ/mol/nm 2 on only the ligand to relax protein side chains. Each equilibrated system was submitted to a 10 ns production run. The temperature was kept at 298 K using a Langevin thermostat , and the pressure was kept at 1 bar with a Berendsen barostat . The nonbonded cutoff distance was set to 0.9 nm, and the simulation was integrated with a time step of 2 fs with the SHAKE algorithm to constrain the bond lengths of bonds involving hydrogen with a relative geometrical tolerance of 10 -6 . The translational and rotational center-of-mass motion is removed every 1000 steps. Trajectories were printed every 5 ps in the production simulation for analysis.