Biophys J, August 2001, p. 751-766, Vol. 81, No. 2

Are Proteins Well-Packed?

Jie Liang^* and Ken A. Dill

 ^*Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60607-7052 and  Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94143-1204

The average packing density inside proteins is as high as in crystalline solids. Does this mean proteins are well-packed? We go beyond average densities, and look at the full distribution functions of free volumes inside proteins. Using a new and rigorous Delaunay triangulation method for parsing space into empty and filled regions, we introduce formal definitions of interior and surface packing densities. Although proteins look like organic crystals by the criterion of average density, they look more like liquids and glasses by the criterion of their free volume distributions. The distributions are broad, and the scalings of volume-to-surface, volume-to-cluster-radius, and numbers of void versus volume show that the interiors of proteins are more like randomly packed spheres near their percolation threshold than like jigsaw puzzles. We find that larger proteins are packed more loosely than smaller proteins. And we find that the enthalpies of folding (per amino acid) are independent of the packing density of a protein, indicating that van der Waals interactions are not a dominant component of the folding forces.

Biophys J, August 2001, p. 751-766, Vol. 81, No. 2
© 2001 by the Biophysical Society   0006-3495/01/08/751/16  $2.00

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