title: Fibrillation-prone conformations of the amyloid-β-42 peptide at the gold/water interface.
abstract: Proteins in the proximity of inorganic surfaces and nanoparticles may undergo profound adjustments that trigger biomedically relevant processes, such as protein fibrillation. The mechanisms that govern protein-surface interactions at the molecular level are still poorly understood. In this work, we investigate the adsorption onto a gold surface, in water, of an amyloid-β (Aβ) peptide, which is the amyloidogenic peptide involved in Alzheimer's disease. The entire adsorption process, from the peptide in bulk water to its conformational relaxation on the surface, is explored by large-scale atomistic molecular dynamics (MD) simulations. We start by providing a description of the conformational ensemble of Aβ in solution by a 22 μs temperature replica exchange MD simulation, which is consistent with previous results. Then, we obtain a statistical description of how the peptide approaches the gold surface by multiple MD simulations, identifying the preferential gold-binding sites and giving a kinetic picture of the association process. Finally, relaxation of the Aβ conformations at the gold/water interface is performed by a 19 μs Hamiltonian-temperature replica exchange MD simulation. We find that the conformational ensemble of Aβ is strongly perturbed by the presence of the surface. In particular, at the gold/water interface the population of the conformers akin to amyloid fibrils is significantly enriched, suggesting that this extended contact geometry may promote fibrillation.
authors.affiliation: Center S3, CNR Institute of Nanoscience, via Campi 213/A, 41125 Modena, Italy. stefano.corni@nano.cnr.it luca.bellucci@nano.cnr.it.
authors.forename: Luca
authors.identifier: http://orcid.org/0000-0001-6707-108X
authors.initials: L
authors.lastname: Bellucci
authors.affiliation: SISSA-Scuola Internazionale Superiore di Studi Avanzati, via Bonomea 265, 34136 Trieste, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussi
authors.affiliation: Center S3, CNR Institute of Nanoscience, via Campi 213/A, 41125 Modena, Italy. stefano.corni@nano.cnr.it luca.bellucci@nano.cnr.it and Department of Physics and Astronomy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Felice
authors.affiliation: Center S3, CNR Institute of Nanoscience, via Campi 213/A, 41125 Modena, Italy. stefano.corni@nano.cnr.it luca.bellucci@nano.cnr.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Corni