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A postreductionist framework for protein biochemistry

Nature Chemical Biology volume 7, pages 331–334 (2011)Cite this article

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As biochemistry ventures out from its reductionist roots, concentration effects and high surface-to-volume ratios will challenge our current understanding of biological systems, with colloidal and surface chemistry leading to new insights and approaches. How must our thinking change, what new tools will we need and how will these new tools be developed?

The differences between studying a dilute solution of an isolated protein and understanding its behavior in vivo come down to coping with three new characteristics: greater system complexity, high concentrations and abundant, heterogeneous surface area. From a thermodynamic standpoint, the greater complexity means that we must recognize that many protein characteristics are system properties and are not properties of the protein. Thermodynamically, high concentrations force us to be comfortable discussing the chemical activity of the protein and not just its concentration. Finally, the presence of diverse surfaces in vivo compels us to consider how a protein interacts with those surfaces and the effect of the interaction on its chemical potential.

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Figure 1: To-scale drawing of E. coli cytosol illustrates the problems faced in developing a framework for postreductionist biochemistry: the high concentration of a diverse mixture of proteins leads to a chemically complicated system in which there is little bulk water.
Figure 2: Proximity energy profile for the approach of two identical proteins with a net charge of 10 and charge-dipole amplitude of 0.01 kilojoules mol−1 coulomb−1 debye−1.

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Authors and Affiliations

  1. Borries Demeler is in the Department of Biochemistry, the University of Texas Health Science Center, San Antonio, Texas, USA.,

    Tom Laue

  2. Tom Laue is in the Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, New Hampshire, USA.,

    Borries Demeler

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  1. Tom Laue
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Correspondence to Tom Laue or Borries Demeler.

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Competing interests

T.L. is co-owner of Spin Analytical, which is producing the new analytical ultracentrifuge.

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Laue, T., Demeler, B. A postreductionist framework for protein biochemistry. Nat Chem Biol 7, 331–334 (2011). https://doi.org/10.1038/nchembio.575

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