Note that even with flip moves, there are some accepted moves that do not result in an actual transition, as seen from the difference between the number of accepted moves accepted and the number actual transitions. This is probably because during the NCMC relaxation for a small percentage of moves, the ligand is able to relax back to its previous binding mode with acceptable work values. 4.5. MD/NCMC method gives reasonable population estimates for different JNK1 and CDK2 inhibitors. After optimizing and validating our protocol with ligand 1, we decided to test our MD/NCMC method on additional ligands. Figure shows the probability of the two binding states during the course of MD/NCMC simulations for ligands 2-4.