Meny

Javascript verkar inte påslaget? - Vissa delar av Lunds universitets webbplats fungerar inte optimalt utan javascript, kontrollera din webbläsares inställningar.
Du är här

Protein dynamics: aggregation and mechanical unfolding

Författare:
  • Simon Mitternacht
Publiceringsår: 2009
Språk: Engelska
Sidor:
Dokumenttyp: Doktorsavhandling

Sammanfattning

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.

Disputation

2009-04-17
13:30
Lecture hall F, Department of Theoretical Physics
  • Guido Tiana (Dr)

Nyckelord

  • Biophysics
  • Monte Carlo simulations
  • All-atom protein models
  • Mechanical unfolding
  • Protein aggregation

Övriga

Published
  • Anders Irbäck
  • ISBN: 978-91-628-7714-9

Box 117, 221 00 LUND
Telefon 046-222 00 00 (växel)
Telefax 046-222 47 20
lu [at] lu [dot] se

Fakturaadress: Box 188, 221 00 LUND
Organisationsnummer: 202100-3211
Om webbplatsen