Abstract
A brief review is given of the use of molecular surface area in estimations of hydrophobic forces and of their influence on protein structure. Molecular area can be used as an estimate of the free energy of transfer of a solute between solvents of differing polarity. Area changes that occur on forming secondary and tertiary structural units are examined including the possible uses of such estimates in algorithms for folding peptide chains.
In 1975Lumry andRosenberg introduced the concept of mobile defects in discussing protein dynamics with particular reference to hydrogen exchange experiments (25). This idea is examined quantitatively in this paper. A first order approach is taken by assuming volume changes to occur by isometric expansion and contraction of the small cavities that occur as packing defects in the structures of all proteins. The positions and mean volume of these defects can be derived from the known X-ray structure using the Voronoi construction. The volume fluctuations of these cavities are assumed to follow a normal distribution leading to a probability of expansion to any preset value, vo. The standard deviation of the fluctuation, σ, is related to the mean isothermal compressibility of the protein and is a characteristic of that particular molecule (8). The parameter vo is related to the process being considered and should be the same for all proteins. For hydrogen exchange it should be related to the volume of a water molecule. For fluorescence quenching it would reflect the molecular volume of the quencher. The theory has been applied to myoglobin and pancreatic trypsin inhibitor. Reasonable agreement with hydrogen exchange data for the slowly exhanging amide protons can be obtained, but there is difficulty with the rapidly exchanging protons and access to the protein surface. No explicit account has yet been taken of the changes in exchange rate due to primary or secondary structure, factors which will particularly effect the surface positions.
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Richards, F.M. Packing defects, cavities, volume fluctuations, and access to the interior of proteins. Including some general comments on surface area and protein structure. Carlsberg Res. Commun. 44, 47 (1979). https://doi.org/10.1007/BF02906521
DOI: https://doi.org/10.1007/BF02906521