Scaffold Diversity Analysis of Compound Data Sets Using an Entropy‐Based Measure

Abstract

Scaffold diversity analysis of compound databases has multiple applications in medicinal chemistry and drug discovery including library design, compounds acquisition, virtual screening and assessment of structure-activity-relationships. The scaffold diversity is commonly measured based on frequency counts. Further information can be obtained by considering the specific distribution of the molecules in those scaffolds. To this end, we introduce in this work the use of an entropy-based information metric to assess the scaffold diversity of compound data sets. As a test case we analyzed the scaffold diversity of 16 data sets of active compounds comparable in size targeting five protein classes of interest in drug design. The diversity was also assessed in terms of frequency counts and scaffold retrieval curves. The entropy-based information metric takes into account the frequency distribution of the different scaffolds and is a complementary measure of scaffold diversity enabling a more comprehensive analysis.

Molecular Scaffold Analysis of Natural Products Databases in the Public Domain

“…A remarkable feature of the scaffolds of Johnson and Xu to compare compound collections is that molecules classified in a scaffold do not lie in any other chemotype class (39). The MEQI approach has been extensively used to classify compound collections (23,31,40,41).…”

“…The distribution of scaffolds for each database was analyzed using CSR curves (23,35,42,43). To generate the CSR curves, the scaffolds are ordered by their frequency of occurrence (most to least common).…”

“…Therefore, SSE values closer to 1.0 indicate large diversity within the n most populated scaffolds. This measure is discussed elsewhere (23,41).…”

“…In this work, we compiled five publicly available natural products databases and performed a comprehensive scaffold analysis including a recently introduced measure for scaffold diversity analysis (23). The natural products were compared with an in-house collection of compounds obtained from combinatorial chemistry and with a general screening library.…”

Comparative Cheminformatic Analysis of Inhibitors of DNA Methyltransferases

“…Scaffold recovery curves were obtained for each of the nine sub-groups (Figure 6). Table 3 summarizes the results of scaffold diversity for each sub group as determined by different metrics [26].…”