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Tytuł:
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How Cu(II) binding affects structure and dynamics of α-synuclein revealed by molecular dynamics simulations.
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Autorzy:
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Savva L; School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK.
Platts JA; School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK.. Electronic address: .
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Źródło:
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Journal of inorganic biochemistry [J Inorg Biochem] 2023 Feb; Vol. 239, pp. 112068. Date of Electronic Publication: 2022 Nov 13.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: New York, Elsevier.
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MeSH Terms:
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alpha-Synuclein*/metabolism
Molecular Dynamics Simulation*
Copper/chemistry ; Binding Sites ; Protein Structure, Secondary
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Contributed Indexing:
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Keywords: Copper; Implicit solvent; Metal ion; Molecular dynamics; Parkinson's disease; Synuclein
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Substance Nomenclature:
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0 (alpha-Synuclein)
789U1901C5 (Copper)
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Entry Date(s):
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Date Created: 20221120 Date Completed: 20221226 Latest Revision: 20230223
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Update Code:
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20240104
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DOI:
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10.1016/j.jinorgbio.2022.112068
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PMID:
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36403437
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We report accelerated molecular dynamics simulations of α-Synuclein and its complex with two Cu(II) ions bound to experimentally determined binding sites. Adding two Cu(II) ions, one bound to the N-terminal region and one to the C-terminus, decreases size and flexibility of the peptide while introducing significant new contacts within and between N-terminus and non-Aβ component (NAC). Cu(II) ions also alter the pattern of secondary structure within the peptide, inducing more and longer-lasting elements of secondary structure such as β-strands and hairpins. Free energy surfaces, obtained from reweighting the accelerated molecular dynamics boost potential, further demonstrate the restriction on size and flexibility that results from binding of copper ions.
Competing Interests: Declaration of Competing Interest The authors confirm that no conflict of interest exists in this work.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
