Amyloid beta oligomers: how pH influences over trimer and pentamer structures?

Carla A. Paredes-Rosan, Diego E. Valencia, Haruna L. Barazorda-Ccahuana, Jorge A. Aguilar-Pineda, Badhin Gómez

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The aggregation of proteins in the brain is one of the main features of neurodegenerative diseases. In Alzheimer’s disease, the abnormal aggregation of Aβ-42 is due to intrinsic and extrinsic factors. The latter is due to variations in the environment, such as temperature, salt concentration, and pH. We evaluated the effect of protonation/deprotonation of residues that are part of trimeric and pentameric oligomers at pH 5, pH 6, and pH 7. Molecular dynamics simulation at 200 ns in the canonical ensemble was implemented. The results have revealed that histidine, glutamic acid, and aspartic acid residues showed a protonation/deprotonation effect in oligomers. The root mean square deviation analysis was used to analyze the structural stability at different pHs. We found an increase in hydrophobicity in the side chains of the trimer, while in the pentamer, the structural instability of a compact structure at pH 5 caused the hydrophobic core to open, revealing the hydrophobic region to the environment. At this point, we believe that conformational changes mediated by pH are essential in the aggregation of Aβ-42 oligomers.

Original languageEnglish
Article number1
JournalJournal of Molecular Modeling
Volume26
Issue number1
DOIs
StatePublished - 1 Jan 2020

Keywords

  • Alzheimer’s disease
  • Amyloid beta 42
  • Molecular dynamic

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