Biophysical tools for structure-based drug design.

The emerging understanding of the structural basis of biological function has made possible a new technology of rational drug design. This technology uses a combination of modeling and intensive computational tools, but also relies critically on direct structural methods for verification and to provide direction for new leads. The present work illustrates applications of this technology to ligand design for several model systems, including iterative modeling and crystallographic design of streptavidin ligands, ranking of streptavidin ligands using comparative molecular field analysis and ranking of thermolysin inhibitors using Poisson-Boltzman methods.