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Updated: Aug 23, 2026

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Influence of conservation on calculations of amino acid covariance in multiple sequence alignments
Anthony A Fodor1, Richard W Aldrich
1Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5345, USA.
Abstract:
It has long been argued that algorithms that find correlated mutations in multiple sequence alignments can be used to find structurally or functionally important residues in proteins. We examined the properties of four different methods for detecting these correlated mutations. On both simple, artificial alignments and real alignments from the Pfam database, we found a surprising lack of agreement between the four correlated mutation methods. We argue that these differences are caused in part by differing sensitivities to background conservation. Correlated mutation algorithms can be envisioned as "filters" of background conservation with each algorithm searching for correlated mutations that occur at a different background conservation frequency.
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