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Review
. 1997 Jan 10;265(1):68-84.
doi: 10.1006/jmbi.1996.0712.

Protein binding versus protein folding: the role of hydrophilic bridges in protein associations

Affiliations
Review

Protein binding versus protein folding: the role of hydrophilic bridges in protein associations

D Xu et al. J Mol Biol. .

Abstract

The role of hydrophilic bridges between charged, or polar, atoms in protein associations has been examined from two perspectives. First, statistical analysis has been carried out on 21 data sets to determine the relationship between the binding free energy and the structure of the protein complexes. We find that the number of hydrophilic bridges across the binding interface shows a strong positive correlation with the free energy; second, the electrostatic contribution of salt bridges to binding has been assessed by a continuum electrostatics calculation. In contrast to protein folding, we find that salt bridges across the binding interface can significantly stabilize complexes in some cases. The different contributions of hydrophilic bridges to folding and to binding arise from the different environments to which the involved hydrophilic groups are exposed before and after the bridges are formed. These groups are more solvated in a denatured protein before folding than on the surface of the combining proteins before binding. After binding, they are buried in an environment whose residual composition can be much more hydrophilic than the one after folding. As a result, the desolvation cost of a hydrophilic pair is lower, and the favorable interactions between the hydrophilic pair and its surrounding residues are generally stronger in binding than in folding. These results complement our recent finding that while hydrophobic effect in protein-protein interfaces is significant, it is not as strong as that observed in the interior of monomers. Taken together, these studies suggest that while the types of forces in protein-protein interaction and in protein folding are similar, their relative contributions differ. Hence, association of protein monomers which do not undergo significant conformational change upon binding differs from protein folding, implying that conclusions (e.g. statistics, energetics) drawn from investigating folding may not apply directly to binding, and vice versa.

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