Structure modeling and dynamics driven mutation and phosphorylation analysis of Beta-amyloid peptides

Abstract

The most common characteristics of diverse age-related neurodegenerative diseases are aggregation and accumulation of the misfolded protein in the brain. Alzheimer׳s disease (AD) is one of these protein conformational diseases. Extracellular accumulation of amyloid β (Aβ) is one the neuropathological hallmarks of Alzheimer disease. Various studies have shown that mutation in specific hydrophobic region of Aβ protein inhibit the formation of β sheet, thus aggregation of this protein is stalled. The identification of such mutation in Aβ protein can help us in elucidating the etiology of sporadic Aβ. In our study we have selected three positions: 19ILU, 21ALA and 41ILU in Aβ protein based on their hydrophobic nature and substituted them with PRO ( βSheet breaker). The effects of the substitutions were analysed using molecular dynamics simulation studies. The results validated that the mutations in the specified regions change the hydrophobicity of the protein and the βsheet formation was declined to zero per cent.

Mutation-based structural modification and dynamics study of amyloid beta peptide (1–42): An in - silico-based analysis to cognize the mechanism of aggregation

“…Other residues apart from the alpha helical regions acquire the coil conformation. Proline acts as a β sheet breaker, which is most common in amyloid β fibrils, that attains a conformation in diseased condition [28] . Insertion of bulky groups or proline within the β sheet regions is effective in inhibition of aggregation as shown in Fig.…”

Structural elucidation of estrus urinary lipocalin protein (EULP) and evaluating binding affinity with pheromones using molecular docking and fluorescence study

“…Therefore, the EULP has inherent provision for post-translational modification. Further the modification would be useful to predict the various cellular functions regulating protein activity31.…”