The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the protein's aggregation. Here we predict its free energy landscape in aqueous solution by using bias exchange metadynamics. All our findings are consistent with experimental data. N17 populates four main kinetic basins, which interconvert on the microsecond time-scale. The most populated basin (about 75%) is a random coil, with an extended flat exposed hydrophobic surface. This might create a hydrophobic seed promoting Huntingtin aggregation. The other main populated basins contain helical conformations, which could facilitate N17 binding on its cellular targets. (C) 2011 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Conformations of the Huntingtin N-term in aqueous solution from atomistic simulations / Rossetti, G; Cossio, P; Laio, Alessandro; Carloni, P.. - In: FEBS LETTERS. - ISSN 0014-5793. - 585:19(2011), pp. 3086-3089. [10.1016/j.febslet.2011.08.036]

Conformations of the Huntingtin N-term in aqueous solution from atomistic simulations

Laio, Alessandro;
2011-01-01

Abstract

The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the protein's aggregation. Here we predict its free energy landscape in aqueous solution by using bias exchange metadynamics. All our findings are consistent with experimental data. N17 populates four main kinetic basins, which interconvert on the microsecond time-scale. The most populated basin (about 75%) is a random coil, with an extended flat exposed hydrophobic surface. This might create a hydrophobic seed promoting Huntingtin aggregation. The other main populated basins contain helical conformations, which could facilitate N17 binding on its cellular targets. (C) 2011 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
2011
585
19
3086
3089
Rossetti, G; Cossio, P; Laio, Alessandro; Carloni, P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/14095
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