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Description
Molecular mimicry, where foreign and self-peptides contain similar epitopes, can induce autoimmune responses. Identifying potential molecular mimics and studying their properties is key to understanding the onset of autoimmune diseases such as type 1 diabetes mellitus (T1DM). Previous work identified pairs of infectious epitopes (EINF) and T1DM epitopes (ET1D) that demonstrated sequence homology; however, structural homology was not considered. Correlating sequence homology with structural properties is important for streamlining translational investigation of potential molecular mimics. This work compares sequence homology with structural homology by calculating the structures and electrostatic potentials of 35 pairs of epitopes identified in previous work. For each epitope pair, the root mean square deviation (RMSD) was calculated between their predicted structures, and their electrostatic potentials were compared. Structures were predicted using AlphaFold and I-TASSER. A structural match of EINF and ET1D pairs was considered successful if the RMSD was < 1.5 Å. AlphaFold found a 76.5% success rate and I-TASSER 82.35%. Of the pairs that could not be structurally matched (< 3 residues aligned), AlphaFold found four unique pairs, and I-TASSER two. Both agreed on four structurally unmatched pairs. Despite structural differences, these four EINF/ET1D pairs show similar electrostatic distributions, indicating they may still bind to the same protein targets, major histocompatibility complex molecules, for T1DM. These findings suggest that searching for epitope pairs using sequence homology, a much less computationally demanding approach, leads to strong candidates for further study.
Publication Date
4-1-2025
Keywords
molecular mimicry, autoimmune disease, type 1 diabetes mellitus, T1DM, epitope homology, sequence homology, structural homology, electrostatic potential, RMSD, AlphaFold, I-TASSER, epitope prediction, peptide structure, major histocompatibility complex, bioinformatics, translational research, autoimmune response, computational biology
Recommended Citation
Wilkins, Joshua; Facelli, Julio C.; Gardner, Ryan; Mistry, Sejal; and Gouripeddi, Ramkiran, "Molecular Level Understanding of Epitope Binding Mimicry Leading to Onset of Type 1 Diabetes (T1D)" (2025). 2025 Honors College Research Symposium. 35.
https://digital.library.ncat.edu/honorscollegesymposium25/35