Classification of amino acids based on statistical results of known structures and cooperativity of protein folding.

It has been found that the 20 kinds of amino acids have different frequencies of occurrence in alpha,beta, and coil structures [P. Y. Chou and G. D. Fasman, Biochemistry 13, 211 (1974)]. Based on more known structures of proteins, frequencies for each amino acid in alpha and beta secondary structures are recalculated. Next step, under the approximation ignoring the chain connectivity of proteins, energy parameters to form alpha and beta secondary structures for each amino acid are obtained. According to the hydrophobicity and energies in alpha and beta secondary structures, 20 kinds of amino acids are classified. The results suggest that dividing amino acids to five or nine groups is desirable. At last, a protein model considering both two-body hydrophobic interaction and one-body energy to form secondary structures, hydrophobic-polar alphabeta model, is introduced. It is shown that the consistency among various energy terms makes the cooperativity of protein folding closer to the experiments.