Thermodynamic Fluctuations and Function in Proteins

  • Alan Cooper
  • David T. F. Dryden
Part of the Progress in Mathematics book series (NSSA)


Although protein molecules have reasonably well defined structures under physiological conditions, with the elegantly complex and functionally refined architectures revealed by X-ray crystallography, there is an additional level of complexity which we must now consider. For proteins and other biological macromolecules are inherently dynamic objects which are in a perpetual state of conformational fluctuation. Superimposed upon the average conformation of any molecule is a spectrum of atomic motions covering a range of frequencies and amplitudes, and involving both the uncorrelated movement of single atoms or groups and the more orchestrated motions of larger structural domains. With a few notable exceptions it was not until the 1970’s that most of us began (reluctantly in many cases!) to accept this point of view, despite a significant amount of experimental evidence that could not be interpreted in terms of the hitherto conventional static picture of protein structures (Cooper,1976). It is not hard to understand the basis for this reluctance: protein structures are difficult enough to comprehend as it is without the additional complications of visualising them in perpetual motion as well; and why bother if we can understand protein function in terms of their static structures anyway? But, of course, the answer is that we can’t. Many aspects of protein function, not least the various aspects of enzyme catalysis which concern us here, are inherently dynamic processes which would not, and could not take place in the absence of fluctuations. There has been considerable theoretical progress in recent years, notably in the area of computer simulation of macromolecular dynamics (McCammon & Harvey, 1987) which, together with some of the experimental advances, have been discussed elsewhere here. Our role here is to review the subject from a more general thermodynamic viewpoint and to consider some of the possible implications to our understanding of protein function.


Partition Function Biological Macromolecule Energy Fluctuation Molecular Collision Macroscopic Object 
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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Alan Cooper
    • 1
  • David T. F. Dryden
    • 1
  1. 1.Department of ChemistryGlasgow UniversityGlasgowScotland, UK

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