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Coarse-Grained Simulation Approaches for Protein Integration and Translocation via the Sec Translocon

Citation

Niesen, Michiel Jacobus Maria (2018) Coarse-Grained Simulation Approaches for Protein Integration and Translocation via the Sec Translocon. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z91N7ZBS. https://resolver.caltech.edu/CaltechTHESIS:04052018-112428695

Abstract

This thesis describes coarse-grained approaches for simulating the co-translational integration and translocation of proteins via the Sec translocon, which is a key step in the biogenesis of membrane and secretory proteins. We present a coarse-grained simulation approach that is capable of simulating minute-timescale dynamics while retaining sufficient chemical and structural detail to capture sequence-specific interactions. The model is validated through comparison to existing experimental data and applied to characterize the forces that act on nascent proteins and drive successful integration and translocation. We also apply coarse-grained simulations of the integration of multi-spanning membrane proteins to understand the effect of sequence modifications on expression levels. We uncover the link between integration efficiency and observed expression levels for membrane proteins, and utilize coarse-grained simulations to predict sequence modifications that improve heterologous overexpression.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Sec translocon; membrane protein; molecular dynamics; protein translocation; membrane protein integration
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Miller, Thomas F.
Thesis Committee:
  • Shan, Shu-ou (chair)
  • Clemons, William M.
  • Goddard, William A., III
  • Miller, Thomas F.
Defense Date:23 March 2018
Record Number:CaltechTHESIS:04052018-112428695
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:04052018-112428695
DOI:10.7907/Z91N7ZBS
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.celrep.2016.07.042DOIArticle adapted for Ch. 4
https://doi.org/10.1371/journal.pcbi.1005427DOIArticle adapted for Ch. 2
https://doi.org/10.1074/jbc.M117.813469DOIArticle adapted for Ch. 3
ORCID:
AuthorORCID
Niesen, Michiel Jacobus Maria0000-0002-9255-6203
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10794
Collection:CaltechTHESIS
Deposited By: Michiel Niesen
Deposited On:18 Apr 2018 22:18
Last Modified:04 Oct 2019 00:20

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