Collaborative Research: Unlocking the mechanism of tRNA translocation through the ribosome using large-scale molecular simulation

Joan And Sanford I. Weill Medical College Of Cornell University, New York NY

Investigators

Abstract

Ribosomes are molecular factories residing inside living cells responsible for reading genetic instructions originating in DNA and assembling proteins from amino acids based on these instructions. Ribosomes read genetic information by latching onto a long string-like molecule messenger RNA that contains the genetic instructions for one single protein molecule. The ribosome must convert the language of RNA into the language of protein. To accomplish this, the ribosome employs another class of RNA molecules called transfer RNA molecules, which convert the RNA alphabet into the protein alphabet. Much of ribosome research over the past 40 years has focused on the movement of transfer RNAs through the ribosome; however, the precise molecular mechanism has eluded researchers. It is only recently, with powerful supercomputers, single molecule imaging, and relevant atomic resolution structures, that this question can be addressed in atomic detail. Understanding how the ribosome works may lead to breakthroughs in the development of bio-inspired nanoscale computers, helping to fuel the nanotech industry. Understanding the ribosome may also lead to new insights into the origin of life and the origin of the genetic code. The objective of this project is to study mechanism of ribosome head swivel using an integrated approach of molecular simulations and single molecule imaging. In head swivel, the head pivots around the neck, while the messenger RNA strand moves simultaneously around the neck and the transfer RNA moves through the inside of the ribosome. Simulations will be performed to understand the global motions of the ribosome occurring during head swivel. Detailed simulations will produce predictions for the energy landscape of head swivel. Fluorescent labels will be placed on the ribosome to monitor head swivel as a function of time using single molecule experiments. These same labels can be added into simulations to obtain comparisons between simulation and experiment and provide atomistic interpretations of the experiments. This project is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Computational Physics Program in the Division of Physics in the Mathematical and Physical Sciences Directorate.