Investigating translational control of the ribosome using molecular dynamics simulations

The ribosome is one of the most basic cellular machines and is ubiquitous in all living cells, responsible for the translation of genes into functional proteins. The central task of the ribosome is to promote peptide-bond transfer reaction by precisely aligning substrates of protein synthesis in ribosomal peptidyl-transferase center (PTC). To guarantee translation fidelity and cell survival, protein synthesis by the ribosome is tightly controlled by cofactors and a range of biological processes. In this thesis, we aim to investigate four translational control mechanisms that bring the ribosomal PTC into focus: (1) abolishment of ribosomal translation by the antibiotic action of macrolide drugs. (2) programmable translation arrest modulated by regulatory nascent peptides. (3) ribosomal discrimination of the chirality of amino acids within PTC. (4) translational control by EttA (energy-sensing translational throttle A) under energy-depleted cellular conditions. We employ computational approaches and collaborate closely with experimentalists. Our joint efforts advanced the understanding of translational control by the interplay of ribosome and cofactors. Our results may promote novel design of next generation antibiotic drugs because the bacterial ribosome is the main antibiotic drug target.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics & Computnl Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2016

Author dc:creator

• Liu, Bo

Contributors dc:contributor

• Schulten, Klaus
• Jin, Hong
• Luthey-Schulten, Zaida
• Tajkhorshid, Emad

• antibiotic
• ribosome
• molecular dynamics simulation
• molecular dynamics flexible fitting
• translation control

Statement dc:rights

• 2016 by Bo Liu. All rights reserved.

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/92991

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/92991