PREDICTION OF PEPTIDE AFFINITY TO HLA DRB1-ASTERISK-01401

Hydrogen bonding between conserved amino acids in the HLA DR and the p eptide backbone of the ligand both provide the majority of free energy of binding and force the peptide ligands to adopt a similar extended conformation. Consequently the corresponding side chains of all peptid es interact with similar pockets in the binding site. For peptides of a common length the contribution of the peptide backbone can be treate d as a constant and the differential affinity can be viewed as a simpl e sum of the side chain interactions. These can be quantified by measu ring the effects of each 1 of the naturally occurring amino acids in t he context of a simplified polyalanine backbone containing an aromatic amino acid to orient the peptide unequivocally in the binding site. T he dataset of the relative contributions can be used to predict quanti tatively the affinity of any peptide sequence.