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Modeling of platinum-aryl interaction with amyloid-β peptide
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Turner, Matthew A. P., Platts, James A. 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. doi:10.1021/acs.jctc.5b01045 ISSN 1549-9618.
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Official URL: http://dx.doi.org/10.1021/acs.jctc.5b01045
Abstract
Ligand field molecular mechanics (LFMM), density functional theory (DFT), and semiempirical 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 modeling 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 310 K 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: | Journal Article | ||||||
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Subjects: | Q Science > QD Chemistry | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||
Library of Congress Subject Headings (LCSH): | Ligand field theory, Density functionals | ||||||
Journal or Publication Title: | Journal of Chemical Theory and Computation | ||||||
Publisher: | American Chemical Society | ||||||
ISSN: | 1549-9618 | ||||||
Official Date: | 12 January 2016 | ||||||
Dates: |
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Volume: | 12 | ||||||
Number: | 3 | ||||||
Number of Pages: | 8 | ||||||
Page Range: | pp. 1385-1392 | ||||||
DOI: | 10.1021/acs.jctc.5b01045 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Date of first compliant deposit: | 10 May 2016 | ||||||
Date of first compliant Open Access: | 12 January 2017 | ||||||
Funder: | Cardiff University, University of Edinburgh, National Institute of General Medical Sciences (U.S.) (NIGMS), Chemical Computing Group (Great Britain) | ||||||
Grant number: | P41-GM103311 (NIGMS) |
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