Deciphering the message in protein sequences: tolerance to amino acid substitutions.

By J. Bowie, J. Reidhaar-Olson, Wendell A. Lim, R. Sauer. 1990

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Protein sectors: evolutionary units of three-dimensional structure (2009, background): “…interpretation:moreconserved positions tend to be located in the core of the protein or at functional surfaces, and less conserved positions tend to occur on the remainder of the protein surface (Figures 1B and 1C) (Bowie et al., 1990; Chothia and Lesk, 1982; Lesk and Chothia, 1982).”
Prediction of amino acid sequence from structure (2000, background): “However, the large amount of sequence degeneracy expected ~ Bowie et al., 1990 ! and observed for many protein families suggests that this analysis is limited, and potentially misleading.”
Evolution-Based Functional Decomposition of Proteins (2015, unknown): “…known but poorly understood properties of proteins: (i) sparsity , such that only a fraction of the amino acids are functionally critical (21; 55), and (ii) distributed cooperativity , such that folding and function can depend on the coupled action of amino acids linking distantly positioned…”
Evolvability as a function of purifying selection in TEM-1 β-lactamase. (2015, unknown): “Overall, these studies suggest that the function of proteins is insensitive to the vast majority of amino acid changes (Bowie et al., 1990).”