Frustration of protein folding from in vitro to in vivo

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 .

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

2018

Author dc:creator

• Zhang, Yi

Contributors dc:contributor

• Pogorelov, Taras
• Gruebele, Martin
• Luthey-Schulten, Zan
• Rienstra, Chad
• Shukla, Diwakar

• protein folding
• molecular dynamics

Statement dc:rights

• Copyright 2018 Yi Zhang

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/101788

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/101788