De Novo Design of Ligands for Metal Separation - Final Report - 09/15/1996 - 09/14/2000

This application focuses on the development of appropriate computation tools and parameters for the de novo design of selective metal ligands. We have developed a successful suite of tools for computer-aided design of ligands for receptors of known three-dimensional structure (structure-based design), including the prediction of affinity. Adaptation of the algorithms to place donor atoms at appropriate geometrical locations surrounding the metal of interest, rather than filling up a cavity with donor/acceptor atoms placed optimally to interact with a protein active site, is straightforward. Appropriate geometrical parameters for metals can be derived from crystal structures and force constants adapted from recent advances in theories of metal-ligand interactions. The practical goal is computer-aided design of ligands which would be selective for one metal over another with a predicted selectivity ratio and affinity