Weakly Polar Interactions in Proteins

Weakly Polar Interactions in Proteins A. Aromatic Amino Acids 

In the next four subsections, we shall describe the results of statistical surveys of single crystal X-ray and protein crystallographic data bases of atomic coordinates. These surveys document the existence of statistically significant preferences of certain three-dimensional geometric arrange- 

Normalized distance distribution function of the polar coordinate r for all protein atom-aromatic ring contacts as defined by the coordinate system depicted in Pig. 8 ( 10 A). Each value of the distance distribution function was normalized for sample size by dividing the observed frequency by r2. 

The distribution of values of the equatorial angle / is not determined by intrinsic geometric considerations, and all possible values of f are equally probable. However, unfavorable spatial overlap of electron orbitals determine the observed distribution of the variable f . Thus, the distribution of values of f is nearly uniform over its entire range (0° f 360°) with the following notable exceptions The presence of the Cp—Cy bond in tyrosine, phenylalanine, and tryptophan makes values of / = 0° unlikely, and = 180° in tyrosine is partially blocked by the phenolic hydroxyl group. Finally, the five-membered ring of tryptophan partially blocks values of j between 180° and 360°. 

The most widely used test for comparing observed and expected frequencies (or for examining the goodness of fit of the sample to the expected distribution) is called the x2 test it is defined by 

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Burley SK, Petsko GA. Weakly polar interactions in proteins. Protein Chem 1988 39 125-192. 

Weakly polar interactions in proteins and protein-ligand complexes are frequently phenomenologically analyzed and classified in terms of the interacting partners (36). This especially includes interactions with x-sys-tems, such as the NH-T, OH-T, or CH-ir interaction (37, 38), aromatic-aromatic interactions (parallel t-t stacking versus edge-to-face interaction), and the cation-T interaction (39). All of these can mostly be rationalized in terms of electrostatic interactions outlined above that is, they involve interactions between monopoles, dipoles, and quadrupoles (permanent and induced). A more distinct character can be attributed to metal complex-ation, which can play a significant role in individual cases of protein-ligand interactions, as for example in metalloenzymes (2,40, 41). 

An extensive series of review papers and research papers has been published by Tanford on protein denaturation. The stability of protein structure has been discussed in several articles by Privalov, with particular attention paid to the small globular proteins. Conformational behavior is dependent on the inter- and intramolecular forces experienced by these macromolecules. Weakly polar interactions in proteins play an important role and have been discussed by Burley and Petsko. Gurd and Rothgeb have described the motions observed in these nonquiescent macromolecules. Studies of the calorimetrically determined dynamics of complex unfolding transitions in proteins have been reviewed by Freire et al ... 

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