Binding Patterns Associated Aß-HSP60 p458 Conjugate to HLA-DR-DRB Allele of Human in Alzheimer's Disease: An In...

Alzheimer's disease (AD) is a complex, irreversible, progressive brain disorder, which diminishes memory in a slow pace and thinking skills; ranked third by experts. It is a complex disorder that involves numerous cellular and subcellular alterations. The pathogenesis of AD is still unknown, but for better understanding, we proposed an in silico analysis to find out the binding patterns associated with HSP60. Several experimental conclusions have been drawn to understand the actual mechanism behind the forming of aggregation due to misfolding. Protein misfolding disorder is experimentally identified by the accumulation of protein aggregates at the intracellular or extracellular region of brain that adversely affects the cell functioning by disrupting the connection between the cells and ultimately leading to cell death. To unravel the mystery behind the mechanism of AD through computational approach, the current proposal shows the designing of Aß-HSP60 p458 conjugate followed by secondary structure analysis, which is further targeted to HLA-DR-DRB allele of human. The antigenicity of Aß (1-42) peptide is the major concern in our study predicted through PVS server, which provides an insight into the immunogenic behavior of Aß peptide. The mechanism involved in the interaction of HSP60-Aß conjugate with HLA-DR-DRB allele considering the fact that Aß (1-42) is highly immunogenic in human and interactions evoked highly robust T-cell response through MHC class II binding predictions. It was assisted by molecular dynamics simulation of predicted HSP60 structure followed by validation through Ramachandran plot analysis and protein-protein interaction of Aß (1-42) with HSP60.