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Updated: Aug 17, 2026

Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
Published on: March 12, 2020
Protein structure similarity clustering (PSSC) and natural product structure as inspiration sources for drug
Frank J Dekker1, Marcus A Koch, Herbert Waldmann
1Department of Chemical Biology, Max-Planck Institute of Molecular Physiology, Otto-Hahn Str. 11, D-44227 Dortmund, Germany.
Abstract:
Finding small molecules that modulate protein function is of primary importance in drug development and in the emerging field of chemical genomics. To facilitate the identification of such molecules, we developed a novel strategy making use of structural conservatism found in protein domain architecture and natural product inspired compound library design. Domains and proteins identified as being structurally similar in their ligand-sensing cores are grouped in a protein structure similarity cluster (PSSC). Natural products can be considered as evolutionary pre-validated ligands for multiple proteins and therefore natural products that are known to interact with one of the PSSC member proteins are selected as guiding structures for compound library synthesis. Application of this novel strategy for compound library design provided enhanced hit rates in small compound libraries for structurally similar proteins.
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