Table 1.
HLA associations seen carbimazole, methimazole and propylthiouracil across populations.
Fig 1.
MHCcluster output for risk and control alleles.
Specificity tree shows clustering of alleles and heat map shows the similarity between the binding motifs of each B allele, comparing known risk and possible risk (B*38:01) alleles (highlighted in blue) with selected controls. The scale shows the distance between the alleles, with red (0) showing very similar binding motifs and white (1) showing dissimilar binding motifs. Trees to the left and above the matrix show the hierarchical clustering of the different B alleles.
Fig 2.
Multiple sequence alignment for risk and control alleles.
(a) Multiple sequence alignment for risk alleles B*27:05 and B*38:02, possible risk allele B*38:01 and selected controls B*15:01, B*40:06 B*46:01, B*51:01 and B*54:01. (b) Focusing on positions 65–83. Positions 67 and 80 highlighted in red.
Fig 3.
Molecular docking poses for methimazole.
a) Top scoring docking poses of methimazole for B*38:02_M and B*27:05_S risk alleles (red), B*38:01_M non-associated allele (orange) and the control alleles (blue) B*15:01_S, B*40:06_M, B*46:01_M, B*51:01_S and B*54:01_M, using peptide binding groove search space and top3 pockets search space for AutoDockFR. b-i) Docking poses showing interacting residues as sticks for B*27:05 (b) and B*38:02 (c) risk alleles, B*38:01 (d) suspected risk allele and control alleles B*15:01 (e), B*40:06 (f), B*46:01 (g), B*51:01 (h) and B*54:01 (i). Positions 67 and 80 are shown in red, with measurements between ligands and side chain shown in yellow (Å).
Table 2.
Summary of molecular docking positions for methimazole.
Fig 4.
Molecular docking poses for propylthiouracil.
a) Top scoring docking poses of propylthiouracil for B*38:02_M and B*27:05_S risk alleles (red), B*38:01_M non-associated allele (orange) and the control alleles (blue) B*15:01_S, B*40:06_M, B*46:01_M, B*51:01_S and B*54:01_M, using peptide binding groove search space and top3 pockets search space for AutoDockFR. b-i) Docking poses showing interacting residues as sticks for B*27:05 (b) and B*38:02 (c) risk alleles, B*38:01 (d) suspected risk allele and control alleles B*15:01 (e), B*40:06 (f), B*46:01 (g), B*51:01 (h) and B*54:01 (i). Positions 67 and 80 are shown in red, with measurements between ligands and side chain shown in yellow (Å).
Table 3.
Summary of molecular docking positions for propylthiouracil.
Fig 5.
Boxplots for methimazole and propylthiouracil.
Boxplots showing docking scores for 100 poses searching the peptide binding groove, using both methimazole (MMZ) and propylthiouracil (PTU) for each of the alleles.
Table 4.
Summary of Thr80 interactions for investigated ligands.