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

Investor logo

Warning

This publication doesn't include Faculty of Economics and Administration. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
Authors

KOZMON Stanislav TVAROŠKA Igor

Year of publication 2015
Type Article in Periodical
Magazine / Source Chemical papers
MU Faculty or unit

Central European Institute of Technology

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
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.