Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802; email:
Annu Rev Biophys. 2016 Jul 5;45:345-69. doi: 10.1146/annurev-biophys-070915-094153. Epub 2016 May 23.
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.
蛋白质稳定性和功能的调节始于蛋白质合成过程中，核糖体将信使 RNA 翻译成新生多肽。涉及新生蛋白质的共翻译过程包括折叠、与其他大分子结合、酶修饰以及通过膜的分泌。实验表明，核糖体将氨基酸添加到延伸的新生链的速度会影响这些过程的效率，这些速度的改变可能导致疾病，包括某些类型的癌症。在这篇综述中，我们讨论了分子模拟获得的共翻译过程的最新见解，以及如何结合不同的计算方法来在多个尺度上理解共翻译过程，以及这些模拟所揭示的新情况。最后，我们提出了在未来几年中，该研究领域的计算方法可以解决的有趣问题。
