ABSTRACT
Structure-based ligand design is fascinating and challenging. This chapter focuses on approach to computer-aided ligand design. It is based on the docking of a diverse set of molecular fragments into the active site of a macromolecular target and on the use of a combinatorial strategy to connect them to form candidate ligands. Ligand-design programs are being developed at an ever increasing rate and some are related to various aspects of ligand design approach. The approach for ligand design is based on the combinatorial selection of molecular fragments optimally docked on the protein binding site to form a population of diverse candidate ligands. The developed program for computational combinatorial ligand design requires as input atomic coordinates and partial charges of the protein atoms, as well as the coordinates of the multiple copy simultaneous search minima and the individual contributions to the free energy of binding.
