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Modeling of platinum-aryl interaction with amyloid-β peptide

Turner, Matthew, Platts, James Alexis and Deeth, Robert J. 2016. Modeling of platinum-aryl interaction with amyloid-β peptide. Journal of Chemical Theory and Computation 12 (3) , pp. 1385-1392. 10.1021/acs.jctc.5b01045

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Abstract

Ligand field molecular mechanics (LFMM), density functional theory (DFT) and semi-empirical PM7 methods are used to study the binding of two Pt(II)-L systems to an N-terminal fragment of the amyloid-β peptide, where L = 2,2-bipyridyl or 1,10-phenanthroline. Molecular dynamics simulations are used to explore the conformational freedom of the peptide using LFMM combined with AMBER molecular mechanics parameters. We establish a modelling protocol, allowing for identification and analysis of favorable platinum-binding modes and peptide conformations. Preferred binding modes are identified for each ligand investigated; metal coordination occurs via Nε in His residues for both ligands - His6ε-His13ε and His6ε-His14ε for the bipyridyl and phenanthroline ligands, respectively. The observed change in binding mode for the different ligands suggests that the binding mode of these platinum-based structures can be controlled by the choice of ligand. In the bipy systems, Boltzmann population at 310K is dominated by a single conformer, while in the phenanthroline case, three conformations make significant contributions to the ensemble. The relative stability of these conformations is due to the inherent stability of binding platinum via Nε in addition to subtle H-bonding effects.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Chemistry
Subjects: Q Science > QD Chemistry
Additional Information: PDF uploaded in accordance with publisher's policies at http://www.sherpa.ac.uk/romeo/issn/1549-9618/ (accessed 22.01.15).
Publisher: ACS
ISSN: 1549-9618
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 12 January 2016
Last Modified: 04 Jun 2017 01:19
URI: http://orca.cf.ac.uk/id/eprint/85477

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