It is useful to be able to quantify diversity in order to determine the diversity of a given library or set of molecules and to compare the diversity of libraries. In biological systems, there are obviously upper limits on the geometry of pharmacophores which can be accommodated in receptor sites. The sensitivity of biological activity to the distances between centres in the pharmacophore will depend upon the receptor and the values of the distances. This gives 20 ways of choosing 3 centres. The pharmacophore key is too large to be routinely stored for each molecule and in this work it is calculated when required for molecules, mixtures or entire libraries.
Most molecules have some rotatable bonds and consequently many low energy conformers.
The use of empirical energy calculations to identify populated low energy conformations is prohibitively time- consuming when considering over 10,000 molecules. The pharmacophores exhibited by all accepted conformers are then deduced and the appropriate bits set in the pharmacophore key, as illustrated below. The pharmacophore key can be conveniently visualized as a 3-dimensional plot known as a pharmacophore plot, in which the X,Y and Z axes are used for the distances between the 3 centres. In ChemDiverse, each pharmacophore is represented as a symbol coded to show the pharmacophore's type using 20 letters. For large libraries, the plot may be too crowded but pharmacophore plots for individual molecules, active molecules, etc. are readily interpreted visually.