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Systems chemical biology

Nature Chemical Biology volume 3, pages 447–450 (2007)Cite this article

The increasing availability of data related to genes, proteins and their modulation by small molecules has provided a vast amount of biological information leading to the emergence of systems biology and the broad use of simulation tools for data analysis. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases and simulation approaches, with the goal of creating systems chemical biology.

Hailed as a departure from the 'reductionist approach,' in which investigators dedicate their efforts to the study of a single gene or protein, systems biology is generally regarded as the 'comprehensive approach.' Large networks describing the regulation of entire genomes, metabolic pathways or signal transduction pathways are analyzed in their totality at different levels of biological organization1. Systems biology, which blends theory, computational modeling and high-throughput experimentation2, has already led to advances in the understanding of cell signaling3, developmental biology4, cell physiology5 and metabolic networks6. However, despite these advances in biological insight, what is currently lacking from these approaches is any holistic understanding of how small molecules affect biological systems. The introduction of cheminformatics tools that can be seamlessly integrated with currently available bioinformatic and cheminformatic databases and biological network simulations and software will be required to move toward a systematic understanding of the way small molecules affect biological systems—a field that we call 'systems chemical biology'.

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Figure 1: A simplified representation of the glyoxylate pathway, extracted from KEGG.
Figure 2: Conceptual representation of the systems chemical biology approach, applied to the glyoxylate pathway.

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Acknowledgements

This work was supported in part by the NIH grant U54 MH074425-01 (T.I.O.) and by the NIH planning grant P20-HG003898 (A.T.). Sandia is operated by Sandia Corporation, a Lockheed Martin Company, for the US Department of Energy under Contract DE-AC04-94AL85000 (J.-L.F. and M.D.R.). The authors express their gratitude to T.K. Allu and D.C. Fara (University of New Mexico) for the PubChem bioassay data analysis.

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Authors and Affiliations

  1. Tudor I. Oprea is in the Division of Biocomputing, MSC11 6145, University of New Mexico School of Medicine, 2703 Frontier NE, Albuquerque, New Mexico 87131, USA. toprea@salud.unm.edu,

    Tudor I Oprea

  2. Alexander Tropsha is in the Laboratory for Molecular Modeling, CB # 7360 Beard Hall, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.,

    Alexander Tropsha

  3. Jean-Loup Faulon and Mark D. Rintoul are at Sandia National Laboratories, PO Box 5800, Albuquerque, New Mexico 87185, USA.,

    Jean-Loup Faulon & Mark D Rintoul

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Competing interests

T.I.O. is the founder and CEO of Sunset Molecular Discovery LLC, which markets small-molecule databases for the pharmaceutical industry. He also serves on the Scientific Advisory Board for ChemDiv, Inc., and he owns stock in AstraZeneca plc.

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Oprea, T., Tropsha, A., Faulon, JL. et al. Systems chemical biology. Nat Chem Biol 3, 447–450 (2007). https://doi.org/10.1038/nchembio0807-447

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