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Recently, genome wide association studies showed that there is a strong association between abacavir-induced serious, idio-syncratic, adverse drug reactions (ADRs) and human leukocyte antigen-B*5701 (HLA-B*5701). Studies also found that ab-acavir-induced ADRs were seldom observed in patients carrying the HLA-B*5801 subtype. HLA-B*5801 of the same sero type (B17) as B*5701 differs by only 4 amino acids from B*5701. It is believed that because of these sequence differences, HLA-B*5801 cannot bind the specific peptides which are required for HLA-B*5701 to stimulate the T cell immune response. Thus, the difference in peptide binding profiles between HLA-B*5701 and B*5801 is an important clue for exploring the mechanisms of abacavir-induced ADRs. VHSE (principal component score vector of hydrophobic, steric, and electronic properties), a set of amino acid structural descriptors, was employed to establish QSAR models of peptide-binding affinities of HLA-B*5701 and B*5801. Optimal linear SVM (support vector machine) models with high predictive capabilities were obtained for both B*5701 and B*5801. The R 2 (coefficient of determination), Q 2 (cross-validated R 2 ), and R PRE 2 (R 2 of test set) of two optimal models were 0.7530, 0.7037, 0.6153 (B*5701) and 0.6074, 0.5966, 0.5762 (B*5801), respectively. For B*5701 and B*5801, the mutations in positions 45 (MET-THR) and 46 (ALA-GLU) have little influence on the selection specificity of the P2 position of the bound peptide. However, the mutation in position 97 (VAL-ARG) greatly influences the selection specificity of the P7 position. HLA-B*5701 prefers the bulky and positively charged amino acids at the P7 position. In contrast, HLA-B*5801 prefers the non-polar hydrophobic amino acids at the P7 position while positively charged amino acids are unfavored.
Recently, the genome wide association studies showed that there is a strong association between abacavir-induced serious, idio-syncratic, adverse drug reactions (ADRs) and human leukocyte antigen-B * 5701 (HLA-B * 5701). Studies also found that ab -acavir-induced ADRs were seldom observed in patients carrying the HLA-B * 5801 subtype. HLA-B * 5801 of the same sero type (B17) as B * 5701 different by only 4 amino acids from B * 5701. that because of these sequence differences, HLA-B * 5801 can not bind the specific peptides which are required for HLA-B * 5701 to stimulate the T cell immune response. Thus, the difference in peptide binding profiles between HLA- B * 5701 and B * 5801 is an important clue for exploring the mechanisms of abacavir-induced ADRs. VHSE (principal component score vector of hydrophobic, steric, and electronic properties), a set of amino acid structural descriptors, was employed to establish QSAR models of peptide-binding affinities of HLA-B * 5701 and B * 5801. Optimal linear SVM (support vector machine) models with high predictive capabilities were obtained for both B * 5701 and B * 5801. The R 2 (coefficient of determination), Q 2 (cross-validated R 2), and R PRE 2 (R 2 of test (B * 5801), respectively. For B * 5701 and B * 5801, the mutations in positions 45 (MET-THR) and 46 (ALA-GLU) have little influence on the selection specificity of the P2 position of the bound peptide. However, the mutation in position 97 (VAL-ARG) greatly influences the selection specificity of the P7 position. HLA- B * 5701 prefers the bulky and positively charged amino acids at the P7 position. In contrast, HLA-B * 5801 prefers the non-polar hydrophobic amino acids at the P7 position while positively charged amino acids are unfavored.