Correlated mutations and residue contacts in proteins
Open accessAbstract
The maintenance of protein function and structure constrains the evolution of amino acid sequences. This fact can be exploited to interpret correlated mutations observed in a sequence family as an indication of probable physical contact in three dimensions. Here we present a simple and general method to analyze correlations in mutational behavior between different positions in a multiple sequence alignment. We then use these correlations to predict contact maps for each of 11 protein families and compare the result with the contacts determined by crystallography. For the most strongly correlated residue pairs predicted to be in contact, the prediction accuracy ranges from 37 to 68% and the improvement ratio relative to a random prediction from 1.4 to 5.1. Predicted contact maps can be used as input for the calculation of protein tertiary structure, either from sequence information alone or in combination with experimental information.
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- Authors
- Göbel, U., Sander, C., Schneider, R., & Valencia, A.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Sander, Chris
- Venue
- Proteins Structure Function and Bioinformatics
- Publisher
- Wiley
- Published
- 1994-04
- Volume
- 18
- Issue
- 4
- Pages
- 309-317
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W2171641243
- Cited by
- 863
- References
- 17
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 22 · 2023: 36 · 2022: 22 · 2021: 42 · 2020: 32 · 2019: 42 · 2018: 36 · 2017: 36 · 2016: 39 · 2015: 30 · 2014: 37 · 2013: 34 · 2012: 48
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- green
- orbilu.uni.lu
- Licence
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Keywords
- correlated mutations, residue contacts, contact map prediction, protein evolution, multiple sequence alignment, protein tertiary structure, protein families, protein structure prediction from sequence
- MeSH terms
- Amino Acid Sequence, Biological Evolution, Mathematical Computing, Models, Genetic, Models, Molecular, Models, Theoretical, Molecular Sequence Data, Mutation, Proteins, Ribonuclease, Pancreatic, Structure-Activity Relationship, Trypsin Inhibitors, Sequence Alignment, Protein Structure, Secondary, Crystallography, X-Ray
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