Unexpected Importance of Aromatic–Aliphatic and Aliphatic Side Chain–Backbone Interactions in the Stability of Amyloids

Dragan B. Ninković, Dušan P. Malenov, Predrag V. Petrović, Edward Brothers, Shuqiang Niu, Michael B. Hall, Milivoj R. Belić, Snežana D. Zarić

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The role of aromatic and nonaromatic amino acids in amyloid formation has been elucidated by calculating interaction energies between β-sheets in amyloid model systems using density functional theory (B3LYP-D3/6-31G*). The model systems were based on experimental crystal structures of two types of amyloids: (1) with aromatic amino acids, and (2) without aromatic amino acids. Data show that these two types of amyloids have similar interaction energies, supporting experimental findings that aromatic amino acids are not essential for amyloid formation. However, different factors contribute to the stability of these two types of amyloids. In the former, the presence of aromatic amino acids significantly contributes to the strength of interactions between side chains; interactions between aromatic and aliphatic side chains are the strongest, followed by aromatic–aromatic interactions, while aliphatic–aliphatic interactions are the weakest. In the latter, that is, the amyloids without aromatic residues, stability is provided by interactions of aliphatic side chains with the backbone and, in some cases, by hydrogen bonds.

Original languageEnglish
Pages (from-to)11046-11053
Number of pages8
JournalChemistry - A European Journal
Volume23
Issue number46
DOIs
Publication statusPublished - 16 Aug 2017

Fingerprint

Amyloid
Aromatic Amino Acids
Density functional theory
Hydrogen
Hydrogen bonds
Crystal structure

Keywords

  • Alzheimer's disease
  • amyloid beta-peptides
  • density functional calculations
  • noncovalent interactions
  • protein–protein interactions

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Unexpected Importance of Aromatic–Aliphatic and Aliphatic Side Chain–Backbone Interactions in the Stability of Amyloids. / Ninković, Dragan B.; Malenov, Dušan P.; Petrović, Predrag V.; Brothers, Edward; Niu, Shuqiang; Hall, Michael B.; Belić, Milivoj R.; Zarić, Snežana D.

In: Chemistry - A European Journal, Vol. 23, No. 46, 16.08.2017, p. 11046-11053.

Research output: Contribution to journalArticle

Ninković, Dragan B. ; Malenov, Dušan P. ; Petrović, Predrag V. ; Brothers, Edward ; Niu, Shuqiang ; Hall, Michael B. ; Belić, Milivoj R. ; Zarić, Snežana D. / Unexpected Importance of Aromatic–Aliphatic and Aliphatic Side Chain–Backbone Interactions in the Stability of Amyloids. In: Chemistry - A European Journal. 2017 ; Vol. 23, No. 46. pp. 11046-11053.
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