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

• Autores: Paredes-Rosan C.A., Valencia D.E., Barazorda-Ccahuana H.L., Aguilar-Pineda J.A., Gómez B.
• Formato: artículo
• Fecha de Publicación: 2020
• Institución: Consejo Nacional de Ciencia Tecnología e Innovación
• Repositorio: CONCYTEC-Institucional
• Lenguaje: inglés
• OAI Identifier: oai:repositorio.concytec.gob.pe:20.500.12390/2611
• Enlace del recurso: https://hdl.handle.net/20.500.12390/2611; https://doi.org/10.1007/s00894-019-4247-5
• Nivel de acceso: acceso abierto
• Materia: Molecular dynamic; Alzheimer’s disease; Amyloid beta 42; http://purl.org/pe-repo/ocde/ford#2.04.01

The aggregation of proteins in the brain is one of the main features of neurodegenerative diseases. In Alzheimer’s disease, the abnormal aggregation of A?-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 A?-42 oligomers. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.