Three-dimensional ligand databases

For many of the computer programs developed for lead discovery or inhibitor optimization, large collections of three-dimensional structures of low molecular weight compounds are required as essential input. The basic source for experimentally-determined structures is

• the Cambridge Structural Database (CSD), containing over 110,000 organic molecules. Its usefulness is limited, however, since most of its compounds are not readily available for carrying out inhibition tests.

• It is more practical to use databases of commercially available compounds such as fine chemicals (about 100,000 molecules), medicinal compounds and drugs. All of these contain models of the compounds obtained by structure-generation programs, that convert two-dimensional connection tables into three-dimensional structures.
  • CONCORD is the most popular of these programs, and has recently been used to convert 5,000,000 organic molecules of the Chemical Abstracts Service Registry file.

  All currently available databases of three-dimensional structures of small molecules are essentially limited to one conformation per substance. It is to be expected that this limitation will be overcome to some extent in coming years.