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Title:Investigating translational control of the ribosome using molecular dynamics simulations
Author(s):Liu, Bo
Director of Research:Schulten, Klaus
Doctoral Committee Chair(s):Schulten, Klaus
Doctoral Committee Member(s):Jin, Hong; Luthey-Schulten, Zaida; Tajkhorshid, Emad
Department / Program:School of Molecular & Cell Bio
Discipline:Biophysics & Computnl Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):ribosome
antibiotic
molecular dynamics simulation
molecular dynamics flexible fitting
translation control
Abstract: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.
Issue Date:2016-05-16
Type:Thesis
URI:http://hdl.handle.net/2142/92991
Rights Information:2016 by Bo Liu. All rights reserved.
Date Available in IDEALS:2016-11-10
Date Deposited:2016-08


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