Files in this item

FilesDescriptionFormat

application/pdf

application/pdfZHANG-DISSERTATION-2018.pdf (29MB)
(no description provided)PDF

Description

Title:Frustration of protein folding from in vitro to in vivo
Author(s):Zhang, Yi
Director of Research:Pogorelov, Taras
Doctoral Committee Chair(s):Gruebele, Martin
Doctoral Committee Member(s):Luthey-Schulten, Zan; Rienstra, Chad; Shukla, Diwakar
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):protein folding
molecular dynamics
Abstract:Protein folding, a ubiquitous and vital biological process, where protein random coil transforms into certain conformation in order to fulfill its function. Misfolded protein which fails to acquire proper shape, not only loses its function, but can also cause fatal diseases. In this dissertation, I will present four case studies involving protein folding investigated through computational modeling and molecular dynamics (MD) simulations. All projects are closely related to experiments, demonstrating the unique role of MD simulations in providing insightful molecular details, testing experimental hypothesis as well as predicting new directions for experimentalists. A brief overview of each chapter is summarized here: Chapter 1 gives brief background information on each of the four project as well as a general introduction on MD simulations, the core methodology used throughout the dissertation. Chapter 2 reports work on a fast protein folder named λ-repressor, where we aim to investigate the different folding kinetics between three mutants of λ-repressor observed in experiments and compare experiments with simulations. Chapter 3 presents protein frustration by disulfide bridges in collaboration with Prof. Norelle Daly’s Lab in Australia. We examined a small cysteine-rich cyclic peptide named MCoTI-II and showed that frustration between certain cysteine residues could impede its folding. Chapter 4 details the construction of an atomic model of cytoplasm and explores the folding of a fast-folding protein (WW domain variant) in a cell-like environment. Chapter 5 reports work on protein recognition by the proteasome, where we investigated protein waste recycling in cells and found that protein re-folding is a vital process in 26S proteasome to initiate protein degradation .
Issue Date:2018-07-06
Type:Text
URI:http://hdl.handle.net/2142/101788
Rights Information:Copyright 2018 Yi Zhang
Date Available in IDEALS:2018-09-27
2020-09-28
Date Deposited:2018-08


This item appears in the following Collection(s)

Item Statistics