Evolution of protein cores. Constraints in point mutations as observed in globin tertiary structures

The amino acid sequences of ten globin chain tertiary structures were aligned and structurally equivalenced by spatial superposition of main-chain C^α atoms. A search was then performed for structurally equivalent residue pairs that were buried in the protein core and that had mutated but maintained similar unmutated environments. Residues with atoms in contact with such central residue pairs define their environments. Such examples of point mutations would represent in vivo site-directed mutagenesis as would be observed in evolution. A search for mutated but exposed equivalent central residues was also performed. The constraints placed on the characteristics of the mutated residues (e.g., side-chain volume, polarity, radius of gyration) allow suggestions for the evolutionary modes of protein core and surface development as well as residue substitution guidelines to maintain structural stability in protein engineering and design.