Homology modeling of AA substitutions with opposing FD_AA scores. Homology modeling was performed using the HLA-DPB1*09:01-HLA-DPA1*02:01 heterodimer with the bound 10-mer peptide MP-10R13 derived from the streptococcal M12 protein.⁴⁷  HLA-DP α and β chains are shown in yellow and blue, respectively, and peptide is shown in green. (A) Comparative analysis of 2 AA substitutions at the peptide-binding residue 35, either nonconservative (F35Y; FD_AA 0.85) or conservative (F35L; FD_AA 0.05). Orange or gray patches indicate hydrophilic or hydrophobic areas at the molecular surface introduced by the side chains of polymorphic residue 35. (B) Comparative analysis of 2 nonconservative AA substitutions at neighboring residues with (D55A; FD_AA 0.73) or without (E56A, with FD_AA −0.04) peptide-binding characteristics. Electrostatic interactions between peptide residue P9, conserved R76 of the HLA-DP α chain, and polymorphic D55 of the HLA-DPB1*09:01 β chain are shown as black dotted lines.