The driving force for co-translational protein folding is weaker in the ribosome vestibule due to greater water ordering.

ABSTRACT: Interactions between the ribosome and nascent chain can destabilize folded domains in the ribosome exit tunnel's vestibule, the last 3 nm of the exit tunnel where tertiary folding can occur. Here, we test if a contribution to this destabilization is a weakening of hydrophobic association, the driving force for protein folding. Using all-atom molecular dynamics simulations, we calculate the potential-of-mean force between two methane molecules along the center line of the ribosome exit tunnel and in bulk solution. Associated methanes, we find, are half as stable in the ribosome's vestibule as compared to bulk solution, demonstrating that the hydrophobic effect is weakened by the presence of the ribosome. This decreased stability arises from a decrease in the amount of water entropy gained u

SUBMITTER: Vu QV 

PROVIDER: S-EPMC8442680 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature