Molecular dynamic studies of amyloid-beta interactions with curcumin and Cu2+ ions
| Authors | |
|---|---|
| Year of publication | 2015 |
| Type | Article in Periodical |
| Magazine / Source | Chemical papers |
| MU Faculty or unit | |
| Citation | |
| Web | 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 |
| Field | Biochemistry |
| Keywords | Alzheimers's disease; amyloid beta; molecular dynamics; curcumin |
| Description | 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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