A MOLECULAR DESIGN SYSTEM BASED ON RECEPTOR STRUCTURES:STUDY ON THE INTERACTIONS BETWEEN RETINOIDS AND THEIR BINDING PROTEINS

The macromolecule anatomy ,ligand-fitting ,docking and other computational chemistry programs have been integrated into BIOS( biomolecular interactions and orientation simulator), to be used on IBM compatible microcomputers as a tool for drug design based on receptor structure and molecular interactiOns. Using the BIOS system ,the cellular serum retinol-binding protein(CRBP) and the epididymal retinoic acid binding protein (E-RABP) were scooped around the ligands in the same intermolecular distance to leave two cavities,which show a similarity in distributions of the aromatic residues. However,the geometry of the two binding sites was quite different.The unraveled binding sites were docked by a serics of retinoids,E-RABP binding site may serve as a template for design of new retinoids.