Structural analyses of the ribosome by hybrid approach

The ribosome is the molecular machine which reads and translates genetic information into proteins in all living cells. Lack of an atomic-resolution structure of the ribosome in its actual functional states prevents our understanding of the ribosome. A hybrid approach overcomes the challenge by combining experimental data from X-ray crystallography and cryo-electron microscopy with computing, permitting one to resolve atomic-level structures of intermediates of the functional ribosome and, thereby, to advance our understanding of ribosome function and the underlying physical mechanisms. In this thesis works we further developed an existing hybrid approach, namely the molecular dynamics flexible fitting (MDFF) method, and apply it to the ribosome. We improved MDFF in two regards, first by incorporating structural symmetry information into the fitting protocol and second by the use of a so-called implicit solvent model. In pursuit of the needed methodological development we participated in the Cryo-EM Modeling Challenge 2010, competing with the MDFF method against other hybrid methods. Two aspects of ribosomal functions were investigated. First we studied bacterial resistance to the antibiotic tetracycline, a study that involved a detail investigation of processes in the ribosome. Second we employed MDFF and molecular dynamics simulations to characterize the dynamics of a ribosome-bound chaperone, called trigger factor.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Chan, Kwok Yan

Contributors dc:contributor

• Schulten, Klaus J.
• Aksimentiev, Aleksei
• Ha, Taekjip
• Peng, Jen-Chieh

• ribosome
• molecular dynamics flexible fitting
• cryo-electron microscopy
• Tet(O)
• tetracycline
• trigger factor
• chaperone

Statement dc:rights

• Copyright 2014 Kwok Yan Chan

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/50422

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/50422