Metal binding to amyloid-β1–42: a ligand field molecular dynamics study

Mutter, Shaun T., Turner, Matthew, Deeth, Robert J. and Platts, James A. (2018) Metal binding to amyloid-β1–42: a ligand field molecular dynamics study. ACS Chemical Neuroscience, 9 (11). pp. 2795-2806. ISSN 1948-7193

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Abstract

Ligand field molecular mechanics simulation has been used to model the interactions of copper(II) and platinum(II) with the amyloid-β1–42 peptide monomer. Molecular dynamics over several microseconds for both metalated systems are compared to analogous results for the free peptide. Significant differences in structural parameters are observed, both between Cu and Pt bound systems as well as between free and metal-bound peptide. Both metals stabilize the formation of helices in the peptide as well as reducing the content of β secondary structural elements compared to the unbound monomer. This is in agreement with experimental reports of metals reducing β-sheet structures, leading to formation of amorphous aggregates over amyloid fibrils. The shape and size of the peptide structures also undergo noteworthy change, with the free peptide exhibiting globular-like structure, platinum(II) system adopting extended structures, and copper(II) system resulting in a mixture of conformations similar to both of these. Salt bridge networks exhibit major differences: the Asp23-Lys28 salt bridge, known to be important in fibril formation, has a differing distance profile within all three systems studied. Salt bridges in the metal binding region of the peptide are strongly altered; in particular, the Arg5-Asp7 salt bridge, which has an occurrence of 71% in the free peptide, is reduced to zero in the presence of both metals.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 26145
Notes on copyright: © 2018 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited
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Depositing User: Shaun Mutter
Date Deposited: 08 Feb 2019 11:13
Last Modified: 03 May 2019 12:26
URI: https://eprints.mdx.ac.uk/id/eprint/26145

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