Abstract
Proteins such as the transcription factor RfaH can change biological function by switching between distinct three-dimensional folds. RfaH regulates transcription if the C-terminal domain folds into a double helix bundle and promotes translation when this domain assumes a β-barrel form. This fold-switch has been also observed for the isolated C-terminal domain, dubbed by us as RfaH-C-terminal domain (RfaH-CTD), and is studied here with a variant of the replica-exchange-with-tunneling approach recently introduced by us. We use the enhanced sampling properties of this technique to map the free-energy landscape of RfaH-CTD and to propose a mechanism for the conversion process.