A novel target-based de novo ligand design by use of pseudomolecular probe

Abstract

Three-dimensional structures of drug target molecules are extremely useful for designing novel ligands. We have developed a novel structure-based de novo design method by the combination of a novel concept of pseudomolecular probe(PMP) and alpha spheres aiming to make the utmost use of the three-dimensional structures of the target molecules. Alpha spheres generated at the binding site give good clues to place molecular fragments at the site. A PMP consisting of a functional group and a supporting group can determine the most appropriate position of the functional group at the binding site. The results have indicated that the strategy works reasonably well in reproducing the structures of the original ligands at the binding sites and have proved that this method can become one of the target-based de novo design methods.