Quantitative sequence-kinetics relationship in antigen-antibody interaction kinetics based on a set of descriptors [corrected].

The interaction between recombinant Fab57P and the coat protein of tobacco mosaic virus was studied using quantitative structure-activity relationship (QSAR) method. The development of quantitative multivariate model has shown to be a promising approach for unraveling protein-protein interactions by designed mutations in peptide sequence. This approach makes it possible to stereo-chemically determine which residue properties contribute most to the interaction. A set of side-chain descriptors was proposed and applied in structural characterization of three positions (positions 142, 145 and 146) in the peptide antigen. Quantitative sequence-kinetics relationship (QSKR) models describing the dissociation rates (log k(d) ) were developed successfully using orthogonal signal correction-partial least squares method. The results showed that peptides will have high log k(d) values when the amino acids in position 142 and 145 have high net charge index, and when residue 145 has high hydrophobicity and residue 146 has low hydrophobicity.

Estimation of affinity of HLA-A*0201 restricted CTL epitope based on the SCORE function.

A set of 70 peptides with affinity for the class I MHC HLA-A*0201 molecule was subjected to quantitative analyses of structure-affinity relationship based on the SCORE function with good results (r(2)=0.6982, q(2)=0.6188, RMS=0.280). Then the 'leave-one-out' cross-validation (LOO-CV) and an outer test set including 18 outer samples were used to validate the QSAR model, and the results show that the QSAR model has good predictability for outside samples. Statistical analysis showed that the hydrophobic and hydrogen bond interaction played a significant role in peptide-MHC molecule binding. The study also provided useful information for structure modification of CTL epitope, and laid theoretical base for molecular design of therapeutic vaccine.