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

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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.

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This study was financially supported by CONCYTEC under Project 139-2015 FONDECYT

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Correspondence to Badhin Gómez.

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This paper belongs to Topical Collection QUITEL 2018 (44th Congress of Theoretical Chemists of Latin Expression)

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Paredes-Rosan, C.A., Valencia, D.E., Barazorda-Ccahuana, H.L. et al. Amyloid beta oligomers: how pH influences over trimer and pentamer structures?. J Mol Model 26, 1 (2020). https://doi.org/10.1007/s00894-019-4247-5

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