Statistical Physics of Protein Folding and Aggregation

Summary, in English

The mechanisms of protein folding and aggregation are investigated by computer simulations of all-atom and reduced models with sequence-based potentials. A quasi local Monte Carlo update is developed in order to efficiently sample proteins in the folded phase. A small helical protein, the B-domain of staphylococcal protein A, is studied using a reduced model. In the thermodynamically favoured topology, energy minimisation leads to a conformation whose root mean square deviation form the experimental structure is 1.8Å. We also study the thermodynamics and kinetics of small fast folding proteins without a clear free-energy barrier between the folded and unfolded states. Analytical calculations using a square well-potential enable us to predict the relaxation time within a factor of two. Finally using an all atom model, we study the aggregation properties of a 7-amino acid fragment of Alzheimer's amyloid beta peptide. We find that the system of three and six such fragments form aggregated structures with a high content of antiparallel beta-sheet structure, which is in line with experimental data.

• Author: Giorgio Favrin
• Department/s: Computational Biology and Biological Physics - Undergoing reorganization
• Publishing year: 2004
• Language: English
• Document type: Dissertation
• Publisher: Lund University
• Topic: Biophysics
• Keywords: Two State; Physics; Fysik; Statistics; operations research; programming; aktuariematematik; programmering; operationsanalys; actuarial mathematics; Statistik; Simulations; Aggregation; Protein Folding; Fysicumarkivet A:2004:Favrin
• Status: Published
• Supervisor: [unknown] [unknown]
• ISBN/ISSN/Other: ISBN: 91-628-6073-9
• Defence date: 19 May 2004
• Defence time: 10:15
• Defence place: N/A
• Opponent: Ulrich H E Hansmann (Associate Professor)