Quasi-orthogonal basis sets of molecular graph descriptors as a chemical diversity measure

In the pharmaceutical industry, the virtual screening of combinatorial libraries is used to rationally select compounds for biological testing from databases of hundreds of thousands of compounds. In addition to structural descriptors, such as fingerprints and pharmacophores, the application of relatively simple structural descriptors traditionally used in quantitative structure-activity studies offers speed and efficiency for rapidly measuring the molecular diversity of such collections. We explore new topological indices computed from the molecular graph as potential structural descriptors for the characterization of molecular diversity. A database of 2000 compounds randomly selected from the National Cancer Institute AIDS database was used to measure the intercorrelation of the descriptors. The initial collection of 240 structural descriptors was reduced to several quasi-orthogonal sets of up to 9 descriptors, using different thresholds for the maximum intercorrelation coefficient.