The structural basis for the fidelity of translation was modeled using computational methods. The flexibility of tRNA was explored using molecular dynamics and making a database of all crystallographic structures for tRNA. The modes of flexibility were compared based upon several metrics. A method for fitting cryo-EM with crystallographic structures was developed (MdMD), and also, for finding pathways between cryo-EM states. Biasing methods in molecular dynamics were used to model the pathway for the proofreading step of ribosomal translation. Atomic models were made for the Pre- and Post- accommodation state of the ribosome. These results indicated a new hypothesis for the mechanism of proofreading. There was no evidence for an induced fit mechanism in the large or small subunit of the ribosome during this step. The tRNA has a differential deformation in the kink during decoding that is based upon whether the tRNA is cognate or near-cognate. This difference in stored energy affects the outcome of proofreading, and the simulations of this step show that the ribosome presents some barriers, which would reject tRNA with insufficient stored energy.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/22553 |
| Date | 26 March 2008 |
| Creators | Caulfield, Thomas R. |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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