COMPARATIVE MOLECULAR-FIELD ANALYSIS OF HAPTENS DOCKED TO THE MULTISPECIFIC ANTIBODY IGE(LB4)

Using comparative molecular field analysis (CoMFA), three-dimensional quantitative structure-activity relationships were developed for 27 ha ptens which bind to the monoclonal antibody IgE(Lb4). In order to obta in an alignment for these structurally very diverse antigens, the comp ounds were docked to a previously modeled receptor structure using the automated docking program AUTODOCK (Goodsell, D. S.; Olson, A. J. Pro teins: Struct., Funct., Genet. 1990, 8, 195-202). Remarkably, this ali gnment method yielded highly consistent QSAR models, as indicated by t he corresponding cross-validated r(2) values (0.809 for a model with c arbon as probe atom, 0.773 for a model with hydrogen as probe atom). C onventional alignment failed in providing a basis for self-consistent CoMFAs. Amino acids Tyr Il 50, Tyr H 52, and Trp H 95 of the receptor appeared to be of crucial importance for binding of various antigens. These findings are consistent with earlier considerations of aromatic residues being responsible for the multispecificity of certain immunog lobulins.