Molecular dynamics study on folding and allostery in RfaH (Proteins: Structure, Function, and Bioinformatics)

Upon being released from the N-terminal domain(NTD), the C-terminal domain(CTD) switches from ?-helix conformation to ?-barrel conformation, which converts RfaH from a transcription factor into an activator of translation. The ?->? conformational change may be viewed as allosteric transition. We use molecular dynamics simulations of coarse-grained off-lattice model to study the thermal folding of NTD, CTD, RfaH and the allosteric transition in CTD. The melting temperatures from the specific heat profiles indicate that the ?-barrel conformation is much more stable than the ?-helix conformation. Two helices in ?-helix conformation have similar thermodynamic stabilities and the melting temperatures for ? sheets show slight dispersion. Under the interaction with NTD, CTD is greatly stabilized and the cooperativity for thermal folding is also significantly improved. The ?->? allosteric transition can be approximately described by a two-state model and three parallel pathways are identified. The transition state ensemble, quantified by a Tanford ?-like parameter, resembles the ?-helix and ?-barrel conformations almost to the same extent. This article is protected by copyright. All rights reserved.