Frustration of protein folding from in vitro to in vivo

Zhang, Yi

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https://hdl.handle.net/2142/101788 Copy

Description

Title

Frustration of protein folding from in vitro to in vivo

Author(s)

Zhang, Yi

Issue Date

2018-07-06

Director of Research (if dissertation) or Advisor (if thesis)

Pogorelov, Taras

Doctoral Committee Chair(s)

Gruebele, Martin

Committee Member(s)

• Luthey-Schulten, Zan
• Rienstra, Chad
• Shukla, Diwakar

Department of Study

School of Molecular & Cell Bio

Discipline

Biophysics & Computnl Biology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(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 .

Graduation Semester

2018-08

Type of Resource

text

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

Copyright and License Information

Copyright 2018 Yi Zhang

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