UNITY 2D fingerprints

We have evaluated the various approaches described above by means of simulated virtual screening searches on the MDL Drug Data Report (MDDR) database. After removal of duplicates and molecules that could not be processed using local software, a total of 102 535 molecules were available for searching. These molecules were represented by 988-bit Tripos Unity 2D fingerprints, and searched using the eleven sets of active compounds detailed in Table 1. 

Table 1 MDDR Activity Classes used in this Study. MPS is the mean pair-wise similarity, computed using the Tanimoto coefficient and Unity 2D fingerprints, averaged over all of the molecules in an activity class.

Unity 2D fingerprints [42] are also based on paths and additionally denote the presence of specific functional groups, rings or atoms. Fingerprints have been used in a number of diversity studies, for example [13, 15,39, 43-46]. 

Matter [45] has also validated a range of 2D and 3D structural descriptors for their ability to predict biological activity and for their ability to be able to sample structurally and biologically diverse datasets effectively. The descriptors examined included Unity 2D fingerprints [42], atom-pairs [47],... 

Figure 13.5. Selection of subsets from the IC93 database using random picking (theoretical expectation and representative experimental result) and maximum dissimilarity selection based on UNITY 2D fingerprints. The percentage of biological classes sampled from the IC93 database is plotted versus the subset size.

Figure 13.6. Percent biological classes covered from the IC93 database versus subset sizes for maximum dissimilarity selections using selected MACCS substructure keys counting up to 1,3.5 or 9 occurrences of a particular fragment key, UNITY 2D fingerprints (Unity2D), and theoretical random selections (Random Jheo).

Schuffenhauer et al. [21] reported a comparative study ofbioisosteric replacements with UNITY 2D fingerprints and FBSS (field-based similarity search) using the Bioster database [22] as a source ofbioisosteric pairs. The authors report that both these 2D and 3D methods provide complementary results that were demonstrated to work synergistically when combined using data fusion. The UNITY fingerprint was reported to be very sensitive to heteroatom replacement. This sensitivity can be overcome somewhat by abstracting the atoms present in a structure into pharmacophoric features. 

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