The dynamic evolution of the PrPC from its NMR-derived conformation to a beta-sheet-rich, aggregation-prone conformation is studied through all-atom, explicit solvent molecular dynamics in different temperature and pH conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach aimed at identifying the key residues for the stabilization and folding of the protein. It is shown that under native conditions the stabilization energy is concentrated in regions of the helices H1 and H3, whereas under misfolding conditions (low pH, high temperature, or mutations in selected sites) it is spread out over helix H2. Misfolding appears to be a rearrangement of the chain that disrupts most of the native secondary structure of the protein, producing some beta-rich conformations with an energy distribution similar to that of the native state.

The Determinants of Stability in the Human Prion Protein: Insights into Folding and Misfolding from the Analysis of the Change in the Stabilization Energy Distribution in Different Conditions / S. Colacino, G. Tiana, R. A. Broglia, G. Colombo. - In: PROTEINS. - ISSN 0887-3585. - 62:3(2006), pp. 698-707.

The Determinants of Stability in the Human Prion Protein: Insights into Folding and Misfolding from the Analysis of the Change in the Stabilization Energy Distribution in Different Conditions

G. Tiana
Secondo
;
R. A. Broglia
Penultimo
;
2006

Abstract

The dynamic evolution of the PrPC from its NMR-derived conformation to a beta-sheet-rich, aggregation-prone conformation is studied through all-atom, explicit solvent molecular dynamics in different temperature and pH conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach aimed at identifying the key residues for the stabilization and folding of the protein. It is shown that under native conditions the stabilization energy is concentrated in regions of the helices H1 and H3, whereas under misfolding conditions (low pH, high temperature, or mutations in selected sites) it is spread out over helix H2. Misfolding appears to be a rearrangement of the chain that disrupts most of the native secondary structure of the protein, producing some beta-rich conformations with an energy distribution similar to that of the native state.
Conformational changes; Human prion protein; Misfolding; Molecular dynamics
Settore FIS/04 - Fisica Nucleare e Subnucleare
Settore FIS/03 - Fisica della Materia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/17462
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