Using PAM Matrices in Sequence Alignments

Abstract

INTRODUCTIONCertain amino acid substitutions commonly occur in related proteins from different species. Because a protein still functions with these substitutions, the substituted amino acids are compatible with protein structure and function. Knowing the types of changes that are most and least common in a large number of proteins can assist with predicting alignments for any set of protein sequences. If related protein sequences are quite similar, they are easy to align, and one can readily determine the single-step amino acid changes. If ancestor relationships among a group of proteins are assessed, the most likely amino acid changes that occurred during evolution can be predicted. This type of analysis was pioneered by Margaret Dayhoff and used by her to produce a type of scoring matrix called a percent accepted mutation (PAM) matrix. This article introduces Dayhoff PAM matrices, explains how they are constructed and how they can be used for sequence alignments, and highlights their strengths and limitations.