Growth vs Diversity: A Time-Evolution Analysis of the Chemical Space.

It is well-known that the number of compounds (both synthesized and theoretical ones) is rapidly increasing. Hence, it would be obvious to affirm that the chemical space is expanding. However, is the chemical diversity of compound libraries growing? In this study, we approach this question by quantitatively assessing the time evolution of chemical libraries in terms of chemical diversity as measured with molecular fingerprints. To tackle this task, we employed innovative cheminformatics methods to assess the progress over time of the chemical diversity of compound libraries available in the public domain. Using the iSIM and the BitBIRCH clustering algorithm, we conclude that, based on the fingerprints used to represent the chemical structures, only an increasing number of molecules cannot be directly translated to diversity for the analyzed libraries. With these tools, we have identified what releases contributed to the diversity of the library and the zones they did. More importantly, the proposed pipeline can be applied to study the evolution of any chemical library and to assess how they are covering the chemical space.