Molecular dynamic studies of amyloid-beta interactions with curcumin and Cu2+ ions

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
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KOZMON Stanislav TVAROŠKA Igor

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Chemical papers
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://www.degruyter.com/view/j/chempap.2015.69.issue-9/chempap-2015-0134/chempap-2015-0134.xml
Doi http://dx.doi.org/10.1515/chempap-2015-0134
Obor Biochemie
Klíčová slova Alzheimers's disease; amyloid beta; molecular dynamics; curcumin
Popis Amyloid-beta (A beta) peptide readily forms aggregates that are associated with Alzheimer's disease. Transition metals play a key role in this process. Recently, it has been shown that curcumin (CUA), a polyphenolic phytochemical, inhibits the aggregation of A beta peptide. However, interactions of A beta peptide with metal ions or CUA are not entirely clear. In this work, molecular dynamics (MD) simulations were carried out to clear the nature of interactions between the 42-residue A beta peptide (A beta-42) and Cu2+ ions and CUA. Altogether nine different models were investigated, and more than 2 mu s of the simulation data were analyzed. The models represent the possible modes of arrangement between A beta-42 and Cu2+ ions and CUA, respectively, and were used to shed light on the A beta-42 conformational behavior in the presence of Cu2+ ions and CUA molecules. Obtained data clearly showed that the presence of a CUA molecule or a higher concentration of copper ions significantly affect the conformational behavior of A beta-42. Calculations showed that the change of the His13 protonation state (A beta(H13 delta)-Cu2+, A beta(H13 delta)-Cu2+-CUA models) leads to higher occurrence of the Asp23-Lys28 salt bridge. Analyzes of trajectories revealed that C-terminal beta-sheet structures occurred significantly less frequently, and CUA promoted the stabilization of the a-helical structure. Further, calculations of the A beta-42 complex with CUA and Cu2+ ions showed that CUA can chelate the Cu2+ ion and directly interact with A beta, which may explain why CUA acts as an inhibitor of A beta aggregation. (C) 2015 Institute of Chemistry, Slovak Academy of Sciences
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