The entropy of a substitution matrix tells you how much it generalizes away from the single sequence it starts with. Read @article{altschul91, author = "Stephen F. Altschul", title = "Amino acid substitution matrices from an information theoretic perspective", pages = "555--565", journal = jmb, volume = "219", year = "1991" } A quick google search found tables relating PAM values and entropy: http://www.psc.edu/biomed/genedoc/gdpid.htm http://www-bioeng.ucsd.edu/research/research_groups/compbio/workshop/Lab_3/matrix_entropy.htm