Here we use a joint sMD/MSM protocol, illustrated in Figure , to evaluate the effect a ligand has on the conformational ensemble of a protein. sMD trajectories are not used directly in the MSMs, but only to push the system towards desired intermediate states. Shorter equilibrium simulations, started from conformations achieved via sMD, are employed to observe transitions from these intermediate configurations, which then are combined to build an MSM that uncovers a fuller picture of protein dynamics.