title: Identification of Binding Modes for Amino Naphthalene 2-Cyanoacrylate (ANCA) Probes to Amyloid Fibrils from Molecular Dynamics Simulations.
abstract: The amino naphthalene 2-cyanoacrylate (ANCA) probe is a kind of fluorescent amyloid binding probe that can report different fluorescence emissions when bound to various amyloid deposits in tissue, while their interactions with amyloid fibrils remain unclear due to the insoluble nature of amyloid fibrils. Here, all-atom molecular dynamics simulations were used to investigate the interaction between ANCA probes with three different amyloid fibrils. Two common binding modes of ANCA probes on Aβ40 amyloid fibrils were identified by cluster analysis of multiple simulations. The van der Waals and electrostatic interactions were found to be major driving forces for the binding. Atomic contacts analysis and binding free energy decomposition results suggested that the hydrophobic part of ANCA mainly interacts with aromatic side chains on the fibril surface and the hydrophilic part mainly interacts with positive charged residues in the β-sheet region. By comparing the binding modes with different fibrils, we can find that ANCA adopts different conformations while interacting with residues of different hydrophobicity, aromaticity, and electrochemical properties in the β-sheet region, which accounts for its selective mechanism toward different amyloid fibrils.
authors.affiliation: State Key Laboratory of Virology, College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.|Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory of Virology, College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.|Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Virology, College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.|Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Dan-Yang
authors.initials: DY
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Virology, College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.|Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Feng-Lei
authors.initials: FL
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Virology, College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.|Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University , Wuhan 430072, P. R. China.|School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology , Wuhan 430081, P. R. China.
authors.forename: Yi
authors.identifier: 0000-0001-7626-0026
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D001665:Binding Sites; D005456:Fluorescent Dyes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D009570:Nitriles / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D005456:Fluorescent Dyes; D009281:Naphthalenes; D009570:Nitriles