Protein dynamics: aggregation and mechanical unfolding
(2009)- Abstract
- The subject of this thesis is protein dynamics. Papers I--IV and VI study either of two different processes: mechanical unfolding and aggregation. Paper V presents a computationally efficient all-atom model for proteins, variants of which are used to perform Monte Carlo simulations in the other papers.
Mechanical unfolding experiments probe properties of proteins at the single molecule level. The only information obtained the experiments is the extension and resisting force of the molecule. We perform all-atom simulations to generate a detailed description of the unfolding process. Papers I and II discuss the mechanical and thermal unfolding of the protein ubiquitin. The principal finding of Paper I is that ubiquitin... (More) - The subject of this thesis is protein dynamics. Papers I--IV and VI study either of two different processes: mechanical unfolding and aggregation. Paper V presents a computationally efficient all-atom model for proteins, variants of which are used to perform Monte Carlo simulations in the other papers.
Mechanical unfolding experiments probe properties of proteins at the single molecule level. The only information obtained the experiments is the extension and resisting force of the molecule. We perform all-atom simulations to generate a detailed description of the unfolding process. Papers I and II discuss the mechanical and thermal unfolding of the protein ubiquitin. The principal finding of Paper I is that ubiquitin unfolds through a well-defined pathway and that the experimentally observed non-obligatory unfolding intermediate lies on this pathway. Paper II compares mechanical unfolding pathways with thermal unfolding pathways. In Paper IV we study the mechanical unfolding of the protein FNIII-10 and find that it has three important, mutually exclusive, unfolding pathways and that the balance between the three can be shifted by changing the pulling
strength.
Paper III describes oligomerization of six-chain systems of the disease-related peptide Abeta(16-22). We find that disordered oligomers of different sizes dominate at high temperatures and as temperature is lowered, larger, more structured, oligomers form. In particular a very stable beta-barrel structure forms. Paper VI is an investigation of the effect of mutations on the folding properties of the peptide Abeta42 from Alzheimer's disease. Small aggregates of this peptide are believedto be important toxic agents. We find that a disease-related mutant peptide, with an elevated aggregation propensity, has a larger conformational diversity than the wild-type peptide, whereas a mutation that is known to inhibit aggregation has the opposite effect. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1314697
- author
- Mitternacht, Simon LU
- supervisor
- opponent
-
- Dr Tiana, Guido, University of Milano, Italy
- organization
- publishing date
- 2009
- type
- Thesis
- publication status
- published
- subject
- keywords
- Monte Carlo simulations, All-atom protein models, Mechanical unfolding, Protein aggregation
- pages
- 161 pages
- defense location
- Lecture hall F, Department of Theoretical Physics
- defense date
- 2009-04-17 13:30:00
- ISBN
- 978-91-628-7714-9
- language
- English
- LU publication?
- yes
- id
- 365b21cb-f29a-46fb-90bd-263c79f80dd4 (old id 1314697)
- date added to LUP
- 2016-04-04 14:21:28
- date last changed
- 2018-11-21 21:19:51
@phdthesis{365b21cb-f29a-46fb-90bd-263c79f80dd4,
abstract = {{The subject of this thesis is protein dynamics. Papers I--IV and VI study either of two different processes: mechanical unfolding and aggregation. Paper V presents a computationally efficient all-atom model for proteins, variants of which are used to perform Monte Carlo simulations in the other papers.<br/><br>
<br/><br>
Mechanical unfolding experiments probe properties of proteins at the single molecule level. The only information obtained the experiments is the extension and resisting force of the molecule. We perform all-atom simulations to generate a detailed description of the unfolding process. Papers I and II discuss the mechanical and thermal unfolding of the protein ubiquitin. The principal finding of Paper I is that ubiquitin unfolds through a well-defined pathway and that the experimentally observed non-obligatory unfolding intermediate lies on this pathway. Paper II compares mechanical unfolding pathways with thermal unfolding pathways. In Paper IV we study the mechanical unfolding of the protein FNIII-10 and find that it has three important, mutually exclusive, unfolding pathways and that the balance between the three can be shifted by changing the pulling<br/><br>
strength.<br/><br>
<br/><br>
Paper III describes oligomerization of six-chain systems of the disease-related peptide Abeta(16-22). We find that disordered oligomers of different sizes dominate at high temperatures and as temperature is lowered, larger, more structured, oligomers form. In particular a very stable beta-barrel structure forms. Paper VI is an investigation of the effect of mutations on the folding properties of the peptide Abeta42 from Alzheimer's disease. Small aggregates of this peptide are believedto be important toxic agents. We find that a disease-related mutant peptide, with an elevated aggregation propensity, has a larger conformational diversity than the wild-type peptide, whereas a mutation that is known to inhibit aggregation has the opposite effect.}},
author = {{Mitternacht, Simon}},
isbn = {{978-91-628-7714-9}},
keywords = {{Monte Carlo simulations; All-atom protein models; Mechanical unfolding; Protein aggregation}},
language = {{eng}},
school = {{Lund University}},
title = {{Protein dynamics: aggregation and mechanical unfolding}},
year = {{2009}},
}