Seminarium Fizyki Materii Skondensowanej

Alzheimer's, Parkinson's, Huntington's, type II diabetes, Mad Cow diseaseetc are associated with protein misfolding. In the case of Alzheimer'sdisease, common toxic species leading to this pathology are the extensivedeposits of fibrillar aggregation of amyloid peptides. Understanding thenature and mechanism of formation of amyloid fibrils plays an importantrole in finding proper treatments. Our study reveals that the fibrilgrowth is governed by the two-stage dock-lock mechanism. In the initialstage a monomer docks onto the underlying fibril, and the locking of amonomer requires a much longer time scale. After the lock stage themonomer adopts the conformation that is commensurate with the underlying lattice. Using lattice and all-atom models, we have obtained the main factors that control the fibril formation process. Namely, in agreementwith experiments, we have shown that fibril formation times of polypeptidechains are strongly correlated with hydrophobicity, Coulomb interactionand the population of the fibril-prone conformation in the monomer state.The higher this population the faster is the fibril growth process andthis dependence may be described by a single exponential function. Ourresult opens a new way to understand the fibrillogenesis of bio moleculesat the monomer level. The role of peptide inhibitors of amyloidaggregation will be briefly discussed.1. P.H. Nguyen, Mai Suan Li, G. Stock, J. E. Straub, and D. Thirumalai, Proc. Natl. Acad. Sci. USA 104, 111-116 (2007)2. Mai Suan Li, D.K. Klimov, J. E. Straub, and D. Thirumalai, J. Chem. Phys. 129, 175101 (2008).3. H. B. Nam, M. Kouza, H. Zung, and Mai Suan Li, J. Chem. Phys. 132, 165104 (2010)4. Mai Suan Li, N.T. Co, G. Reddy, C-K. Hu, and D. Thirumalai, Phys. Rev. Lett. 105, 218101 (2010).5. M.H. Viet, S.T. Ngo, N.S. Lam , and Mai Suan Li, J. Phys. Chem. B 115, 7433 (2011)