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- Title
Curcumin Binding to Beta Amyloid: A Computational Study.
- Authors
Rao, Praveen P. N.; Mohamed, Tarek; Teckwani, Karan; Tin, Gary
- Abstract
Curcumin, a chemical constituent present in the spice turmeric, is known to prevent the aggregation of amyloid peptide implicated in the pathophysiology of Alzheimer's disease. While curcumin is known to bind directly to various amyloid aggregates, no systematic investigations have been carried out to understand its ability to bind to the amyloid aggregates including oligomers and fibrils. In this study, we constructed computational models of (i) A β hexapeptide 16 KLVFFA21 octamer steric-zipper β-sheet assembly and (ii) full-length A β fibril β-sheet assembly. Curcumin binding in these models was evaluated by molecular docking and molecular dynamics ( MD) simulation studies. In both the models, curcumin was oriented in a linear extended conformation parallel to fiber axis and exhibited better stability in the A β hexapeptide 16 KLVFFA21 octamer steric-zipper model ( Ebinding = −10.05 kcal/mol) compared to full-length A β fibril model ( Ebinding = −3.47 kcal/mol). Analysis of MD trajectories of curcumin bound to full-length A β fibril shows good stability with minimum C α-atom RMSD shifts. Interestingly, curcumin binding led to marked fluctuations in the 14 HQKLVFFA21 region that constitute the fibril spine with RMSF values ranging from 1.4 to 3.6 Å. These results show that curcumin binding to A β shifts the equilibrium in the aggregation pathway by promoting the formation of non-toxic aggregates.
- Subjects
ALZHEIMER'S disease treatment; AMYLOID beta-protein; CURCUMIN; BINDING sites; MOLECULAR docking; MOLECULAR dynamics; PHYSIOLOGICAL effects of chemicals
- Publication
Chemical Biology & Drug Design, 2015, Vol 86, Issue 4, p813
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12552