Investigation of molecular interaction and conformational stability of disease concomitant to HLA-DRβ3

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Human leucocyte antigen DRβ3 is associated with specific autoimmune thyroid disease and plays a vital role in the progression of Grave’s disease. The available crystallographic structure of the HLA DRA, DRβ3*0101, was selected and used to generate mutation at position 57 from valine amino acid to Aspartic acid (D), Glutamic acid (E), Alanine (A), and Serine (S) amino acids by computational modeling approach. Mutant models were minimized, and stable conformation was chosen based on the lowest root mean square deviation value. Molecular docking assessed the best binding affinity of ligands C1, C2, C3, and C4 with wild-type and mutant HLA-DRβ3 models. Molecular dynamics simulation studies were executed to evaluate the stability of selected hits with wild-type and mutant dock complexes. The C3 has shown good binding affinity with wild-type and selected mutants; V57A, V57E, and V57D. Structural and molecular dynamics insights reveal the differences between wild-type and mutant-type HLA-DRβ3, which could help design novel antagonist molecules against autoimmune thyroid disorder. Communicated by Ramaswamy H. Sarma