The 20 amino acids translated by the genetic code vary greatly by the physical and chemical properties of their side chains.[1] However, these amino acids can be categorised into groups with similar physicochemical properties.[4] Substituting an amino acid with another from the same category is more likely to have a smaller impact on the structure and function of a protein than replacement with an amino acid from a different category. Consequently, acceptance of point mutations depends heavily on the amino acid being replaced in the mutation, and the replacement amino acid. The PAM matrices are a mathematical tool that account for these varying rates of acceptance when evaluating the similarity of proteins during alignment.