Structure-based De Novo Ligand Design

1 Locating Favourable Positions of Molecular Fragments Within a Binding Site 

An alternative to the energy-based methods such as GRID is to suggest possible binding positions using a knowledge-based approach. Analysis of experimentally determined 

3 Structure-based Design Methods to Design HiV-1 Protease Inhibitors 

An impressive example of the application of structure-based methods was the design of an inhibitor of the HIV protease by a group of scienbsts at DuPont Merck [Lam et al. 1994]. This enzyme is crucial to the replication of the HIV virus, and inhibitors have been shown to have therapeutic value as components of anti-AIDS treatment regimes. The starting point for their work was a series of X-ray crystal structures of the enzyme with a number of inhibitors boimd. Their objective was to discover potent, novel leads which were orally available. Many of the previously reported inhibitors of this enzyme possessed substantial peptide character, and so were biologically unstable, poorly absorbed and rapidly metabolised. 

4 Structure-based Design of Templates for Zeolite Synthesis 

---