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Microscopic origins of entropy, heat capacity and the glass transition in proteins

Nature volume 411, pages 501–504 (2001)Cite this article

Abstract

Internal motion is central to protein folding1, to protein stability through the resulting residual entropy2, and to protein function1,3,4,5,6,7. Despite its importance, the precise nature of the internal motions of protein macromolecules remains a mystery. Here we report a survey of the temperature dependence of the fast dynamics of methyl-bearing side chains in a calmodulin–peptide complex using site-specific deuterium NMR relaxation methods. The amplitudes of motion had a markedly heterogeneous spectrum and segregated into three largely distinct classes. Other proteins studied at single temperatures tend to segregate similarly. Furthermore, a large variability in the degree of thermal activation of the dynamics in the calmodulin complex indicates a heterogeneous distribution of residual entropy and hence reveals the microscopic origins of heat capacity in proteins. These observations also point to an unexpected explanation for the low-temperature ‘glass transition’ of proteins. It is this transition that has been ascribed to the creation of protein motional modes that are responsible for biological activity5,6,7.

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Figure 1: Fast dynamics of methyl-bearing side chains in a calmodulin–peptide complex.
Figure 2: Fast dynamics of methyl-bearing side chains in proteins.
Figure 3: Distribution of the temperatures at which maximal side-chain order is achieved in the calmodulin–peptide complex.
Figure 4: Temperature dependence of the average S 2axis values of methyl-bearing side chains of complexed calmodulin.

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Acknowledgements

We thank S. W. Englander and K. Sharp for discussions. This work was supported by a grant from the NIH.

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Author notes

  1. Andrew L. Lee

    Present address: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7360, USA

Authors and Affiliations

  1. Johnson Research Foundation and Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Andrew L. Lee & A. Joshua Wand

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Correspondence to A. Joshua Wand.

Additional information

The relaxation data has been deposited in the BMRB under accession number 4970.

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Lee, A., Wand, A. Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411, 501–504 (2001). https://doi.org/10.1038/35078119

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