Upon QSAM-based virtual vaccine library project, a reasonable human leukocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocyte (CTL) epitope library was designed. The process is as follows: (a) synthetical property score (SP-score) of amino acids is derived from 516 physicochemical properties by principal component analysis (PCA); (b) based on the SP-score, genetic algorithm-partial least square regression (GA-PLS) is used to construct the quantitative sequence-activity model (QSAM); (c) em-ploying QSAM as evaluation tool, CTL epitopes are optimized by GA; (d) frequency (f) of each amino acid in different position of excellent antigen peptides is calculated; (e) the amino acid in condi-tion of f＞F (F is the random probability, of 1/20 for the natural amino acid) is re-served to be favorable residue type at this position and a structural element of the combinatorial library.

Key words: quantitative sequence-activity model, virtual vaccine library, HLA-A*0201, CTL epitope, genetic algorithm