Letter | Published:

Protein folding and heterogeneity inside globular proteins

Nature volume 272, pages 558560 (06 April 1978) | Download Citation



THE compact globular structure of enzymes and other proteins is the result of a struggle between two major forces. One is the entropy of the protein backbone, which strives towards an open, more random configuration, and the other is the entropy of the water environment, which drives the water-ordering nonpolar sidechains into tightly packed, water-excluding clusters. However, the protein globule would still be relatively flexible were it not for the fact that some polar groups, including those of the backbone are also found in the interior of proteins and make up a skeletal network of hydrogen bonds. The net result is that the interior of a globular protein has continuous clusters of nonpolar sidechains separated by relatively polar regions in which nonpolar sidechains are comparatively infrequent. We have undertaken a study to quantify this structural heterogeneity and to illuminate the folding and packing of sidechains in globular proteins. This study not only uses a simple procedure for analysing protein structure, but provides a method, demonstrated here, for predicting which residues occur in the nonpolar clusters and conversely, the polar or partially polar regions of globular proteins.

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  1. Department of Mathematics, University of Reading, Whiteknights, Reading, UK

  2. Department of Physiology and Biochemistry, University of Reading, Whiteknights, Reading, UK

  3. Department of Biochemistry, University of Manchester, Oxford Road, Manchester, UK



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