Treating each binding site conformation separately; holo-closed, the apo-opened and CMD-opened P-loop conformations, the three replicates of SuMD simulation were concatenated for each ligand, yielding a total of 600 ns simulation time. Filtration was performed before clustering by removal of all SuMD frames with more than 9 Å distance between the ligand and the catalytic cleft. Specifically, a cluster is a protein-ligand complex (a binding pose) formed of at least 100 similar ligand conformations which differ by no more than 1 Å RMSD. The total number of frames in each cluster yields the total residence time (t) for its corresponding protein-ligand binding mode, in which a single SuMD frame is equal to 20 ps of simulation.