Simulating the conformational dynamics of the ATPase complex on proteasome using its free-energy landscape

The AAA+ ATPase complex on proteasome powers its functions through a series of intricate conformational transitions. Here, we describe a procedure to simulate the conformational dynamics of the proteasomal ATPase complex. We first empirically determined the free-energy landscape (FEL) of proteasome and then simulated proteasome’s conformational changes as stochastic transitions on its FEL. We compared the FEL-predicted proteasomal behaviors with experimental measurements and analyzed the map of the ATPase’s global dynamics to gain mechanistic insights into proteasomal degradation. For complete details on the use and execution of this protocol, please refer to Fang et al. (2022).1