PNNL

Abstract

The concepts embodied in de novo structure-based drug design are being adapted for the computer-aided design of metal ion sequestering agents. This adaptation requires the development of methods for (i) generating candidate structures and (ii) evaluating and prioritizing these structures with respect to their binding affinity for a specific guest. This article summarizes recent progress in this area that includes the creation of a new computer software program, called HostDesigner, that can generate and evaluate millions of new molecular structures per minute on a desktop personal computer. Several methods for evaluating the degree of binding site organization in a host structure are presented. An example is provided to demonstrate how these methods have been used to identify ligand architectures that provide enhanced metal ion binding affinity.