Predicting the MHC-Peptide Affinity Using Some Interactive-Type Molecular Descriptors and QSAR Models

The ligand–receptor interaction between some peptidomimetic inhibitors and a class II major histocompatibility complex (MHC)–peptide presenting molecule, the HLA-DR4 receptor, can be modeled using some 3D quantitative structure-activity relationship (QSAR) methods such as the comparative molecular field analysis (CoMFA) and some molecular descriptors using the Cerius2 program. The structures of these peptidomimetic inhibitors can be generated theoretically, and the conformations used in the 3D QSAR studies can be defined by aligning them against the known structure of HLA-DR4 receptor through a least-square fitting procedure. The best CoMFA models can be constructed using the aligned structures of the best fitting result. The principal components analysis (PCA) module of the Cerius2 program can be used to trim outliers of the CoMFA columns generated. Procedures for a direct QSAR analysis using the Cerius2 descriptors and regression analysis by the genetic function module are also presented