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Amino Acid Exchangeability from Experimental Data



L Y. Yampolsky, Arlin Stoltzfus


Amino acid sequence differences between proteins are often interpreted by reference to a pairwise measure of amino acid similarity, based either on observed evolutionary transition probabilities, or on some physicochemical model of effects. However, evolutionary propensities confound real effects on proteins with mutational dynamics imposed by the mechanism of evolution; physicochemical models avoid this confounding effect, but introduce the uncertainty of the underlying hypothetical model. A measure of exchangeability that reliably reflects the role of amino acids in real proteins, yet avoids the confounding effect of mutation, has been computed from results of 9671 experimental exchanges in a set of 12 proteins studied systematically. A frequency distribution of the quantitative effects of amino acid exchanges on protein activity serves as the basis for transforming results of different studies to a common scale, yielding the ?experimental exchangeability? or EX. The power of this approach has been evaluated by a jack-knife procedure in which an EX matrix derived from results for 11 proteins is used to predict the results for the 12th protein. As a predictor of the effects of experimental amino acid exchanges, EX out-performs commonly used amino acid similarity matrices. In combination with models of the mutation spectrum, EX may prove useful in teasing apart the separate influences of mutation and selection on codon usage, amino acid composition, and patterns of protein sequence change.
Journal of Molecular Biology


amino acid replacement, mutagenesis, mutation effects, prediction, protein engineering


Yampolsky, L. and Stoltzfus, A. (2021), Amino Acid Exchangeability from Experimental Data, Journal of Molecular Biology (Accessed May 30, 2024)


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Created October 12, 2021