How frequent are correlated changes in families of protein sequences?

By E. Neher. 1994

A loss-of-function point mutation in a protein is often rescued by an additional mutation that compensates for the original physical change. According to one hypothesis, such compensation would be most effective in maintaining a structural motif if the two mutated residues were spatial neighbors. If this hypothesis were correct, one would expect that many such compensatory mutations have occurred during evolution and that present-day protein families show some degree of correlation in the occurrence of amino acid residues at positions whose side chains are in contact. Here, a statistical theory is presented which allows evaluation of correlations in a family of aligned protein sequences by assigning a scalar metric (such as charge or side-chain volume) to each type of amino acid and calculating correlation coefficients of these quantities at different positions. For the family of myoglobins it is found that there is a high correlation between fluctuations in neighboring charges. The correlation is close to what would be expected for total conservation of local charge. For the metric side-chain volume, on the other hand, no correlation could be found.

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Citations in the corpus

Protein 3D Structure Computed from Evolutionary Sequence Variation (2011, methodology): “alignments can be used to solve this problem [2,5,6,32,33].”
Direct-coupling analysis of residue coevolution captures native contacts across many protein families (2011, background): “s the performance of DCA, but results are robust with respect to precise value of reweighting. A simple measure of correlation between these two columns is the mutual information (MI), defined by Eq. (3) in Methods. As we will show, the MIs turn out to be unreliable predictors of spatial proximity. ”
Protein sectors: evolutionary units of three-dimensional structure (2009, background): “Indeed, several reports have proposed approaches for the calculation of residue covariance, but often with the goal of identifying the pattern of contacts in the three dimensional structure (Gobel et al., 1994; Hamilton et al., 2004; Larson et al., 2000; Neher, 1994; Olmea and Valencia, 1997; Ortiz ”
Fast and Accurate Multivariate Gaussian Modeling of Protein Families: Predicting Residue Contacts and Protein-Interaction Partners (2014, neutral): “onstraint is present by construction in the input data, and that as a consequence we have, for any residue position land any two states aand bwith a6= b: C (l 1)Q+a;(l 1)Q+b = x (l 1)Q+ax (l 1)Q+b 0 (3) i.e. two dierent amino-acids at the same site are anti-correlated. Therefore, we shall let the pa”
Fast pseudolikelihood maximization for direct-coupling analysis of protein structure from many homologous amino-acid sequences (2014, background): “In fact, it has been known for almost 20 years that the evolutionary history leaves a trace in the correlations between amino acids at diﬀerent positions along a protein which contains nontrivial information, see e.g. [2, 3, 4], but before DCA this information was not fully exploitable.”
Correlated mutations contain information about protein-protein interaction. (1997, background): “Several groups have studied correlated mutations: technical differences between different approaches have led to con¯icting conclusions about the nature and intensity of this phenomena (Altschuh et al., 1987, 1988; Go È bel et al., 1994; Neher, 1994; Shindyalov et al., 1994; Taylor & Hatrick, 1994).”
De Novo Structure Prediction of Globular Proteins Aided by Sequence Variation-Derived Contacts (2014, background): “For some time now, the importance of residue-residue contacts in protein structure prediction has been known and explored [1,2,3,4].”
3D Protein Structure Predicted from Sequence (2011, unknown): “In this paper we explore the idea that information gleaned from statistical analysis of multiple sequence alignments can be used to solve this problem [2,5,6,30,31].”
Co-evolving residues in membrane proteins (2007, methodology): “…most commonly used relies on the calculation of a Pearson correlation coefficient to detect alignment positions with similar patterns of amino acid change (Gobel et al., 1994; Kundrotas and Alexov, 2006; Neher, 1994; Olmea and Valencia, 1997; Pollock and Taylor, 1997; Taylor and Hatrick, 1994).”
Determination of network of residues that regulate allostery in protein families using sequence analysis (2006, unknown): “method (Lesk and Chothia, 1980; Altschuh et al., 1987; Neher, 1994; Taylor”