| Abstract: | A systematic study was carried out on mutability of amino acid residues in evolving proteins in relation to their polarity and location within three-dimensional structure of proteins. Exteriority of residue sites is quantitatively defined as accessibility based on their static accessible surface area to solvent water molecule. Residue sites are classified into interior and exterior depending on their accessibility. More frequent substitution on exterior sites is confirmed to be general in eight sets of homologous protein families regardless of their biological functions and of presence or absence of a prosthetic group. Virtually all types of amino acid residues are found to have higher mutabilities on the exterior than in the interior. No correlation between mutability and polarity was observed of amino acid residues in the interior and on the exterior, respectively. Amino acid residues are classified into three depending on their polarity, polar (Arg, Lys, His, Gln, Asn, Asp and Glu), weak polar (Ala, Pro, Gly, Thr and Ser) and nonpolar (Cys, Val, Met, Ile, Leu, Phe, Tyr and Trp). Amino acid replacements during protein evolution are very conservative; 88% and 76% of them in the interior and on the exterior, respectively, are within the same group of the three. Inter-group replacements are such that weak polar residues are replaced more often by nonpolar residues in the interior and more often by polar residues on the exterior. |
