Undersampling is a frequently encountered shortcoming of simulation-based phase space exploration, e.g. numerous examples are pro-vided in . Naturally, one of the underlying reasons for the inadequate representation of the apo state in the case of p38α protein could be insufficient equilibration of the system. Therefore, we probed whether longer simulations would be able to cross the energy barrier and arrive in the true apo state when starting from a holo crystallographic structure with the ligand removed. To explore this, we have extended the p38α apo state simulations started from 3fly by performing 5 independent runs of 1 µs each. The longer simulations indeed showed a transition of the T106 rotamer from its trans state (3fly holo conformer) to the gauche-state observed in the apo 1wfc structure (Fig ). In all 5 independent replicas, the transition occurred within the first 200 ns. After this, no recrossings back to the trans rotameric state were observed, only short lived transitions from the gauche-to gauche+ state occurred.