Insights into Cotranslational Nascent Protein Behavior from Computer Simulations

Abstract

Regulation of protein stability and function in vivo begins during protein synthesis, when the ribosome translates a messenger RNA into a nascent polypeptide. Cotranslational processes involving a nascent protein include folding, binding to other macromolecules, enzymatic modification, and secretion through membranes. Experiments have shown that the rate at which the ribosome adds amino acids to the elongating nascent chain influences the efficiency of these processes, with alterations to these rates possibly contributing to diseases, including some types of cancer. In this review, we discuss recent insights into cotranslational processes gained from molecular simulations, how different computational approaches have been combined to understand cotranslational processes at multiple scales, and the new scenarios illuminated by these simulations. We conclude by suggesting interesting questions that computational approaches in this research area can address over the next few years.