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

Abstract Chemical space is a core and theoretical concept in cheminformatics, and it also has practical applications in drug discovery and other research areas. Chemical space is frequently associated with the number of molecules in the universe (e.g., chemical universe). It is well known that the number of compounds (both synthesized and theoretical ones) is rapidly increasing. It would be obvious to affirm that the chemical space is expanding (as a proxy of growth). But is the chemical diversity of compound libraries growing? In this study, we tackle this question by assessing quantitatively the time evolution of chemical libraries in terms of the 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, just 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 it did.