Molecular dynamics investigations of the α-helix to β-barrel conformational transformation in the RfaH transcription factor.

The C-terminal domain (CTD) of the transcription antiterminator RfaH folds to an α-helix bundle when it interacts with its N-terminal domain (NTD) but it undergoes an all-α to all-β conformational transformation when it does not interact with the NTD. The RfaH-CTD in the all-α topology is involved in regulating transcription whereas in the all-β topology it is involved in stimulating translation by recruiting a ribosome to an mRNA. Because the conformational transformation in RfaH-CTD gives it a different function, it is labeled as a transformer protein, a class that may eventually include many other functional proteins. The structure and function of RfaH is of interest for its own sake, as well as for the value it may serve as a model system for investigating structural transformations in general. We used replica exchange molecular dynamics simulations with implicit solvent to investigate the α-helix to β-structure transformation of RfaH-CTD, followed by structural relaxation with detailed all atom simulations for the best replica. The importance of interfacial interactions between the two domains of RfaH is highlighted by the compromised structural integrity of the helical form of the CTD in the absence NTD. Calculations of free-energy landscape and transfer entropy elucidate the details of the RfaH-CTD transformation process.

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