Computer design of bioactive compounds based on 3-D properties of ligands.

3-D database searching has many uses for a medicinal chemist. It can aid in the design of compounds to probe or to mimic the bioactive conformation of a natural ligand or to fit a hypothetical or experimental structure of a binding site. It also can identify existing molecules that meet these criteria--new uses for old molecules. If one has a database of active compounds, 3-D searching can validate or refute a pharmacophore hypothesis. The CoMFA method of 3DQSAR can be used to forecast the potency of the designed analogs. Also, the integration of CoMFA and 3-D searching concepts provides a framework for the design of a good series for CoMFA. In addition, CoMFA 3DQSAR coefficients provide a model of the binding site to facilitate the design of compounds that fit the pharmacophore and do not hit sterically unfavorable regions.