Simulation Model of Protein Transport and Stabilization

In a previous communication (Linhananta et al., Biophys. J., 2011, 100, 459), we reported results of a simulation model of a protein in solvents with protein-solvent contact energy parameter $\varepsilon _{ps}$, which mimics the effects of osmolytes ( $\varepsilon _{ps}>0$) and denaturants ($% \varepsilon _{ps}<0$ ). Here a model three-helix-bundle (THB) protein in solvents is confined in cylindrical cavity to mimic GroEL/ES. The interior wall is characterized by the protein-wall energy $\varepsilon _{pw}$ , and solvent-wall energy, $\varepsilon _{sw}$. Simulations found a substantial increase in the folding temperature from $T^{\ast }=4.2$, in scaled unit, for THB in vacuum, to $T^{\ast }>6.0$ for confined THB in osmolytes. The model is generalized to THB and solvents confined in two connected cylindrical segments. The bottom segment represents the interior of a GroEL/ES, with the sidewall characterized by the parameters $\varepsilon _{pw}$ and $\varepsilon _{sw}$. The upper segment represents the exterior surrounding the GroEL/ES, with periodic boundary condition on the sidewall. The protein and solvents can move through the channel connecting the two segments. Simulation data reveals new insights on the transport of unfolded proteins into GroEL/ES.