RfaH is a two-domain metamorphic protein involved in transcription regulation and translation initiation. To carry out dual functions, RfaH relies on two coupled structural changes: domain dissociation and fold switching. In the free state, the C-terminal domain (CTD) of RfaH adopts an all- α fold and is tightly associated with the N-terminal domain (NTD). Upon binding to RNA polymerase (RNAP), the domains dissociate and the CTD completely transforms into an all- β fold, while the NTD remains largely, but not entirely, unchanged. We test the idea that a change in the conformation of an extended β-hairpin ( β3- β4) located on the NTD, helps trigger domain dissociation. To this end, we use homology modelling to construct a structure, H 1 , which is similar to free RfaH but with a remodeled β3- β4 hairpin. We then use an all-atom physics-based model enhanced with a dual-basin structure-based potential to simulate domain separation driven by thermal unfolding of the CTD with NTD in a fixed, folded conformation. We apply our model to both free RfaH and H 1 . For H 1 we find, in line with our hypothesis, that the CTD exhibits a lower stability and the domains dissociate at a lower temperature ( T), as compared to free RfaH. We do not, however, observe complete refolding to the all- β state in these simulations, suggesting that a change in β3- β4 orientation aid in, but is not sufficient for, domain dissociation. In addition, we study the reverse fold switch in which RfaH returns from a domain-open all- β state to its domain-closed all- α state. We observe a T-dependent transition rate; fold switching is slow at low T, where the CTD tend to be kinetically trapped in its all- β state, and at high- T, where the all- α state becomes unstable. Consequently, our simulations suggest an optimal T at which fold switching is most rapid. At this T, the stabilities of both folds are reduced. Overall, our study suggests that both inter-domain interactions and conformational changes within NTD may be important for proper functioning of RfaH.