Molecular dynamics study on folding and allostery in RfaH

Upon being released from the N-terminal domain (NTD), the C-terminal domain (CTD) switches from α-helix conformation to β-barrel conformation, which converts RfaH from a transcription factor into an activator of translation. The α→β 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 β-barrel conformation is much more stable than the α-helix conformation. Two helices in α-helix conformation have similar thermodynamic stabilities and the melting temperatures for β sheets show slight dispersion. Under the interaction with NTD, CTD is greatly stabilized and the cooperativity for thermal folding is also significantly improved. The α→β 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 β-like parameter, resembles the α-helix and β-barrel conformations almost to the same extent.