Speaker
Description
Ribosomes are the biomolecular factories in charge of protein synthesis and are thus essential for life as we know it. As peptides are formed one amino acid residue at a time, they must pass through the ribosomal tunnel. The narrowest part of the ribosomal tunnel, the constriction site (CS), is formed by extended loops of ribosomal proteins uL4 and uL22 unlike the rest of the tunnel, which is made up of ribosomal RNA. The nascent peptide comes into close contact with the CS and so the dynamics of the CS may be important to translation. We want to explore the dynamics of the CS and see how it is affected as a nascent peptide approaches it. To investigate this, we performed bias exchange metadynamics simulations where the distance of uL4 and uL22 tips was biased to enhance sampling of the opening and closing of the CS for four systems. Each contained the whole ribosome and polyglycine of varying length (11, 8 or 5 glycines or no peptide at all) attached to tRNA. In this poster I will present results from analyses of these simulations. We show that CS dynamics depend on peptide length and a free energy surface estimate in a principal component subspace shows that a fully closed conformation is not energetically accessible at the simulation temperature. Still, the CS can spontaneously narrow from the equilibrium of around 1 nm to around 0.25 nm, but the narrow states are sparsely populated. These findings contribute to our understanding of the first moments in the life of protein.
