Hidden thermodynamic information in protein amino acid mutation tables

We combine the standard 1992 20×20 substitution matrix based on block alignment, BLOSUM62, with the standard 1982 amino acid hydropathicity scale KD as well as the modern 2007 hydropathicity scale MZ, and compare the results. The 20-parameter KD and MZ hydropathicity scales have different thermodynamic character, corresponding to first- and second-order transitions. The KD and MZ comparisons show that the mutation rates reflect quantitative iteration of qualitative amino acid-phobic and -philic binary 2×10 properties that define quaternary 4×5 subgroups (but not quinary 5×4 subgroups), with the modern MZ bioinformatic scale giving much better results. The quaternary 5-mer MZ 4×5 subgroups are called mutons (Mu5). Among all hydropathicity scales, the MZ scale uniquely exhibits a smooth, deep mutational minimum at its center associated with alanine, glycine, the smallest amino acid, and histidine.