Deciphering Molecular Mimicry: An In Silico Exploration of Heat shock protein 70 Conservation and its Role in Cross-Reactivity.

Abstract

Objectives To evaluate the sequence and structural conservation of heat shock protein 70 (HSP70) across different allergenic sources and to assess its potential role in molecular mimicry- mediated cross- reactivity . Additionally, conserved linear and conformational epitopes potentially involved in immune recognition were identified. Methods An in silico analysis was performed using HSP70 amino acid sequences from multiple allergenic sources, including mites, cockroaches, helminths, fungi, and mammals. Multiple sequence alignment and phylogenetic analyses were conducted to evaluate sequence conservation and evolutionary relationships. Three-dimensional protein structures were generated through homology modelling and assessed using structural validation parameters. Linear and conformational epitopes were predicted using immunoinformatic tools and mapped onto the modelled structures. Results Eighteen HSP70 sequences were analysed, showing an overall identity of 53% and pairwise similarities up to 98.97%. Phylogenetic analysis grouped the proteins into four clades with sequence identity ranging from 63% to 85%. Structural models showed high reliability, with more than 90% of residues located in the most favoured regions of the Ramachandran plot. Epitope prediction identified 35 linear and 27 conformational epitopes with high confidence scores located in conserved regions. Conclusion HSP70 shows high sequence and structural conservation across allergenic sources, suggesting potential cross-reactivity through molecular mimicry. Conserved epitopes may represent relevant targets for diagnostic and therapeutic approaches, although experimental validation is required.