The data available from standard MD simulations might still be insufficient to explore the complete protein conformation ensemble, such as short-lived intermediate states. Efforts have been invested into adaptive sampling protocols to build more robust MSMs in a unsupervised manner . However it is also possible to exploit prior knowledge about key protein conformational states to generate pathways for conformational transitions between them , using for instance steered MD (sMD) simulations. sMD introduces a restraint on the system, biasing it towards a certain conformation . Therefore conformations that are important to protein dynamics but are not sampled easily through equilibrium MD simulations can be accessed.