Applications of environment specific amino acid substitution tables to identification of key residues in protein tertiary structure

Amino acid substitution tables have been calculated for families of homologous proteins of known three-dimensional structures. Amino acids are classified according to residue type, secondary structure, accessibility of the side-chain, and existence of hydrogen bonds from side-chain to other side-chains or peptide carbonyl or amide functions. Distinct patterns of substitution characterize most classes especially where amino-acid residues are both solvent inaccessible and hydrogen-bonded through their side-chains. These tables can be used to identify key residues that are critically important to the three-dimensional structure. They can also be used to identify patterns of amino acids in proteins of unknown three-dimensional structures that are characteristic of globular domains, super-secondary structures or structural motifs.