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Molecular dynamics simulation on the effect of transition metal binding to the n-terminal fragment of amyloid-β

Turner, Matthew, Mutter, Shaun and Platts, James 2019. Molecular dynamics simulation on the effect of transition metal binding to the n-terminal fragment of amyloid-β. Journal of Biomolecular Structure and Dynamics 37 (17) , pp. 4590-4600. 10.1080/07391102.2018.1555490

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We report molecular dynamics simulations of three possible adducts of Fe(II) to the N-terminal 1-16 fragment of the amyloid-β peptide, along with analogous simulations of Cu(II) and Zn(II) adducts. We find that multiple simulations from different starting points reach pseudo-equilibration within 100 to 300 ns, leading to over 900 ns of equilibrated trajectory data for each system. The specifics of the coordination modes for Fe(II) have only a weak effect on peptide secondary and tertiary structure, and we therefore compare one of these with analogous models of Cu(II) and Zn(II) complexes. All share broadly similar structural features, with mixture of coil, turn and bend in the N-terminal region and helical structure for residues 11-16. Within this overall pattern, subtle effects due to changes in metal are evident: Fe(II) complexes are more compact, and are more likely to occupy bridge and ribbon regions of Ramachandran maps, while Cu(II) coordination leads to greater occupancy of the poly-proline region. Analysis of representative clusters in terms of molecular mechanics energy and Atoms-in-Molecules properties indicates similarity of 4-coordinate Cu and Zn complexes, compared to 5-coordinate Fe complex that exhibits lower stability and weaker metal-ligand bonding.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Advanced Research Computing @ Cardiff (ARCCA)
Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
ISSN: 0739-1102
Funders: EPSRC
Date of First Compliant Deposit: 13 December 2018
Date of Acceptance: 28 November 2018
Last Modified: 25 Mar 2020 16:15

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