Correlated mutations and residue contacts in proteins

Göbel, Ulrike; Sander, Chris; Schneider, Reinhard; Valencia, Alfonso

doi:10.1002/prot.340180402

Cited by 816 publications

(671 citation statements)

References 15 publications

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“…Finally, we note that there has been interest in using information about correlated mutations to assist in the prediction of protein tertiary structure (Benner et al 1994a;Gobel et al 1994;Neher 1994;Shindyalov et al 1994;Taylor and Hatrick 1994). Generally, these analyses have been limited to looking at correlations between the residues found in current-day proteins.…”

Section: Resultsmentioning

confidence: 99%

Probabilistic reconstruction of ancestral protein sequences

1996

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Abstract. Using a maximum-likelihood formalism, we have developed a method with which to reconstruct the sequences of ancestral proteins. Our approach allows the calculation of not only the most probable ancestral sequence but also of the probability of any amino acid at any given node in the evolutionary tree. Because we consider evolution on the amino acid level, we are better able to include effects of evolutionary pressure and take advantage of structural information about the protein through the use of mutation matrices that depend on secondary, structure and surface accessibility. The computational complexity of this method scales linearly with the number of homologous proteins used to reconstruct the ancestral sequence.

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Section: Resultsmentioning

confidence: 99%

Probabilistic reconstruction of ancestral protein sequences

1996

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“…The results from this same program were also used as an independent P-strand secondary structure prediction method. Correlated mutations were calculated using the algorithm of Gobel et al (1994). The program takes a multiple sequence alignment of a protein family and tries to decode the observed mutational patterns in order to identify constrained sequence changes.…”

Section: Prediction Methodsmentioning

confidence: 99%

A proposed architecture for the central domain of the bacterial enhancer-binding proteins based on secondary structure prediction and fold recognition

1997

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The expression of genes transcribed by the RNA polymerase with the alternative sigma factor os4 ( E d 4 ) is absolutely dependent on activator proteins that bind to enhancer-like sites, located far upstream from the promoter. These unique prokaryotic proteins, known as enhancer-binding proteins (EBP), mediate open promoter complex formation in a reaction dependent on NTP hydrolysis. The best characterized proteins of this family of regulators are NtrC and NifA, which activate genes required for ammonia assimilation and nitrogen fixation, respectively. In a recent IRBM course ("Frontiers of protein structure prediction," IRBM, Pomezia, Italy, 1995; see web site http://www.mrc-cpe.cam.uk/ irbm-course95/), one of us (J.O.) participated in the elaboration of the proposal that the Central domain of the EBPs might adopt the classical mononucleotide-binding fold. This suggestion was based on the results of a new protein fold recognition algorithm (Map) and in the mapping of correlated mutations calculated for the sequence family on the same mononucleotide-binding fold topology. In this work, we present new data that support the previous conclusion. The results from a number of different secondary structure prediction programs suggest that the Central domain could adopt an alp topology. The fold recognition programs ProFIT 0.9, 3D PROFILE combined with secondary structure prediction, and 123D suggest a mononucleotide-binding fold topology for the Central domain amino acid sequence. Finally, and most importantly, three of five reported residue alterations that impair the Central domain ATPase activity of the E d 4 activators are mapped to polypeptide regions that might be playing equivalent roles as those involved in nucleotidebinding in the mononucleotide-binding proteins. Furthermore, the known residue substitutions that alter the function of the Eos4 activators, leaving intact the Central domain ATPase activity, are mapped on a region proposed to play an equivalent role as the effector region of the GTPase superfamily.

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“…In this study, no correlation was found between residue covariation and residue proximity in the hydrophobic core. However, the possibility of using covariation as an indicator of structural proximity has been tested recently on a number of other protein sequence families, and weak, but possibly useful, correlations have been found in some cases (Gobel et al, 1994;Shindyalov et al, 1994). There is some disagreement as to whether such pairwise correlations provide additional information beyond that of a simple conservation metric, but differences in methodology make comparisons difficult (Taylor & Hatrick,I 994).…”

Section: Discussionmentioning

confidence: 99%

“…A number of recent papers have examined the relationship between residue correlations and structure (Gobel et al, 1994;Neher, 1994;Shindyalov et al, 1994;Taylor & Hatrick, 1994). However, as noted by these authors and others, apparent correlations can also arise from biases in the sequence set.…”

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confidence: 99%

Covariation of residues in the homeodomain sequence family

Clarke

1995

Protein Science

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Homeodomains are 60 amino acid DNA binding domains found in numerous eukaryotic transcription factors. The homeodomain family is a useful system for studying sequence-structure relationships because several hundred sequences are known and the structures of several homeodomains have been determined. Covariation of amino acid residues in the homeodomain family has been investigated to see whether strongly covariant residue pairs can be understood in terms of the structure and function of these domains. Among 16 strongly covariant pairs examined, 2 are explained by the ability to form salt bridges, and 9 appear related to the DNA binding function of the proteins. For the remaining 5 pairs, the rationale for covariance remains unclear and the likelihood of artifactual correlations is discussed in the context of experimental and evolutionary biases in the selection of sequences. No significant correlation was found between covariance and structural proximity in the hydrophobic core.

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Correlated mutations and residue contacts in proteins

Cited by 816 publications

References 15 publications

Probabilistic reconstruction of ancestral protein sequences

Probabilistic reconstruction of ancestral protein sequences

A proposed architecture for the central domain of the bacterial enhancer-binding proteins based on secondary structure prediction and fold recognition

Covariation of residues in the homeodomain sequence family

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