DescriptionThere is now a large body of experimental evidence that the ability of many proteins to reach full functionality in a cell depends strongly on the rate at which individual codons are translated by the ribosome during protein synthesis. This project aims to demonstrate that, counter to conventional wisdom, fast-translating codons can help coordinate co-translational protein folding by minimizing misfolding [O’Brien, Nature Comm. 2014]. To do this we will use a two-step approach: First (Aim 1), we will utilize coarse-grained molecular dynamics simulations in combination with a genetic algorithm to find the optimal codon translation rate profile that maximizes the co-translational folding of a protein. And then (Aim 2) mutate, in silico, fast-translating codon positions to slower rates to test, if as predicted, we observe a concomitant decrease in the amount of co-translational folding. The results of this study will provide a new computational tool for the rational design of mRNA sequences to control nascent proten behavior.
OrganizationThe Pennsylvania State University
Sponsor Virtual OrganizationOSG
Principal Investigator
Edward O'Brien
Field Of ScienceBiophysics