Protein homomers in point-group assembly: symmetry making and breaking are specific and distinctive in their codes of chemical alphabet in side chains.

Oligomerizing to point-group symmetry, protein oligomers need to have the symmetry broken for biologically crucial functions, such as, allosteric regulation, enzyme catalysis, and so forth. In the making of symmetry, based on self assembly, and the breaking of symmetry, based on intermolecular interactions, proteins may manifest, like their other functions, specific scripts over the coding alphabet in side chains. To address the possibility, we analyzed 82 protein homodimers in their C(2)-symmetry-related side chains across noncrystallographic interfaces, to know if they may be identical or distinct in conformation, and thus conserved or broken in symmetry. We find the propensity to conformational mismatch across interfaces correlated with side-chain chemical structure, low to very low in aromatic Trp, Tyr, His, Phe, and Arg, and high to very high in aliphatic Val, Pro, Met, Glu, Ser, Lys, Gln, Asn, and Asp, related not to polarity but, interestingly, to aromaticity of the structure. The organizational plan having aromatics embedded in a hub of aliphatic-nonpolar groups and a surrounding rim of aliphatic-polar groups, called "hotspot," has been known to direct protein-protein interaction. Finding conformational-mismatch propensities of side chains congruous with their specific chemical roles in protein-protein interaction, we propose that aromatic side chains will drive protein homomers to high symmetry, while polar- and nonpolar aliphatic side chains will drive them to the functionally-necessitated breaks of symmetry. Side chains are in their roles as protein-coding alphabet illuminated in the physics, which is discussed.