Table of Contents
Journal of Biophysics
Volume 2011, Article ID 219515, 11 pages
http://dx.doi.org/10.1155/2011/219515
Research Article

Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and X-Ray Data

1School of Chemistry & Biochemistry, Georgia Institute of Technology, 901 Atlantic Avenue, Atlanta, GA 30332-0230, USA
2School of Biology, Georgia Institute of Technology, 901 Atlantic Avenue, Atlanta, GA 30332-0230, USA

Received 27 September 2010; Revised 31 December 2010; Accepted 24 January 2011

Academic Editor: Eaton Edward Lattman

Copyright © 2011 Thomas R. Caulfield et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We examined tRNA flexibility using a combination of steered and unbiased molecular dynamics simulations. Using Maxwell's demon algorithm, molecular dynamics was used to steer X-ray structure data toward that from an alternative state obtained from cryogenic-electron microscopy density maps. Thus, we were able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon molecular dynamics simulations and unbiased simulation methods to identify possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs during translation. Herein, we collected >500 ns of simulation data to assess the global range of motion for tRNAs. Biased simulations can be used to steer between known conformational stop points, while unbiased simulations allow for a general testing of conformational space previously unexplored. The unbiased molecular dynamics data describes the global conformational changes of tRNA on a sub-microsecond time scale for comparison with steered data. Additionally, the unbiased molecular dynamics data was used to identify putative contacts between tRNA and the ribosome during the accommodation step of translation. We found that the primary contact regions were H71 and H92 of the 50S subunit and ribosomal proteins L14 and L16.