There are generally two scenarios that can lead to dissipation and non-overlapping work distributions (SI Figure , S15) or bimodal work distributions (Figure ): In the first scenario the system ends up in the correct end state but during NEQ switches was driven rapidly and accordingly heat was dissipated (friction). Secondly, the system does not end up in the equilibrium end state at the end of the short transition. An example for this second scenario is the Ile78 side chain orientation discussed above.