title: Conformations of the Huntingtin N-term in aqueous solution from atomistic simulations.
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.
authors: German Research School for Simulation Science, FZ-Juelich and RWTH Aachen, Jülich, Germany.
authors: Giulia
authors: G
authors: Rossetti
authors: Pilar
authors: P
authors: Cossio
authors: Alessandro
authors: A
authors: Laio
authors: Paolo
authors: P
authors: Carloni
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D006801:Humans; D000071058:Huntingtin Protein; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012996:Solutions; D014867:Water