Beta-hairpin conformation of fibrillogenic peptides : structure and alpha -beta transition mechanism revealed by molecular dynamics simulations
Articolo
Data di Pubblicazione:
2004
Citazione:
Beta-hairpin conformation of fibrillogenic peptides : structure and alpha -beta transition mechanism revealed by molecular dynamics simulations / I. Daidone, F. Simona, D. Roccatano, R. A. Broglia, G. Tiana, G. Colombo, A. Di Nola. - In: PROTEINS. - ISSN 0887-3585. - 57:1(2004), pp. 198-204.
Abstract:
Understanding the conformational transitions that trigger the aggregation and amyloidogenesis of otherwise soluble peptides at atomic resolution is of fundamental relevance for the design of effective therapeutic agents against amyloid-related disorders. In the present study the transition from ideal -helical to -hairpin conformations is revealed by long timescale molecular dynamics simulations in explicit water solvent, for two well-known amyloidogenic peptides: the H1 peptide from prion protein and the A(12-28) fragment from the A(1-42) peptide responsible for Alzheimer's disease. The simulations highlight the unfolding of -helices, followed by the formation of bent conformations and a final convergence to ordered in register -hairpin conformations. The -hairpins observed, despite different sequences, exhibit a common dynamic behavior and the presence of a peculiar pattern of the hydrophobic side-chains, in particular in the region of the turns. These observations hint at a possible common aggregation mechanism for the onset of different amyloid diseases and a common mechanism in the transition to the -hairpin structures. Furthermore the simulations presented herein evidence the stabilization of the -helical conformations induced by the presence of an organic fluorinated cosolvent. The results of MD simulation in 2,2,2-trifluoroethanol (TFE)/water mixture provide further evidence that the peptide coating effect of TFE molecules is responsible for the stabilization of the soluble helical conformation
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
I. Daidone, F. Simona, D. Roccatano, R. A. Broglia, G. Tiana, G. Colombo, A. Di Nola
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