Theoretical and Computational Chemistry

Exploration of the chemical space of DNA-encoded libraries



DNA-Encoded Library (DEL) technology has emerged as an alternative method for bioactive molecule discovery in medicinal chemistry. It enables simple synthesis and screening of compound libraries of enormous size. Even though it gains more and more popularity each day, there are almost no reports of chemoinformatics analysis of DEL chemical space. Therefore, in this project we aimed to generate and analyze theultra-large chemical space of DEL. Around 2500 DELs were designed using commercially available BBs resulting in 2,5B DEL compounds that were compared to biologically relevant compounds from ChEMBL using Generative Topographic Mapping. This allowed to choose several optimal DELs covering the chemical space of ChEMBL to the highest extent and thus containing the maximum possible percentage of biologically relevant chemotypes. Different combinations of DELs were also analyzed to identify a set of mutually complementary libraries allowing to attain even higher coverage of ChEMBL than it is possible with one single DEL.


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