title: The interaction with gold suppresses fiber-like conformations of the amyloid β (16-22) peptide.
abstract: Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution.
authors.affiliation: Dipartimento FIM, Università di Modena e Reggio Emilia, I-41125, Modena, Italy. luca.bellucci_s3@unimore.it and Centro S3, CNR-NANO Istituto Nanoscienze, I-41125, Modena, Italy. stefano.corni@nano.cnr.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Bellucci
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH-Zurich, Switzerland and Facoltà di Informatica, Istituto di Scienze Computazionali, Università della Svizzera Italiana, CH-6900, Lugano, Switzerland.
authors.forename: Albert
authors.initials: A
authors.lastname: Ardèvol
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH-Zurich, Switzerland and Facoltà di Informatica, Istituto di Scienze Computazionali, Università della Svizzera Italiana, CH-6900, Lugano, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: Parrinello
authors.affiliation: Max Planck Institute for Polymer Research, D-55128 Mainz, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Lutz
authors.affiliation: Max Planck Institute for Polymer Research, D-55128 Mainz, Germany.
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.affiliation: Max Planck Institute for Polymer Research, D-55128 Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weidner
authors.affiliation: Centro S3, CNR-NANO Istituto Nanoscienze, I-41125, Modena, Italy. stefano.corni@nano.cnr.it and Facoltà di Informatica, Istituto di Scienze Computazionali, Università della Svizzera Italiana, CH-6900, Lugano, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Corni
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D036103:Nanotechnology; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D013499:Surface Properties
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22); D006046:Gold