Coevolutionary Analysis of Protein Subfamilies by Sequence Reweighting
By Duccio Malinverni, Alessandro Barducci. 2019
14 citations recorded by the source corpus.
Extracting structural information from sequence co-variation has become a common computational biology practice in the recent years, mainly due to the availability of large sequence alignments of protein families. However, identifying features that are specific to sub-classes and not shared by all members of the family using sequence-based approaches has remained an elusive problem. We here present a coevolutionary-based method to differentially analyze subfamily specific structural features by a continuous sequence reweighting (SR) approach. We introduce the underlying principles and test its predictive capabilities on the Response Regulator family, whose subfamilies have been previously shown to display distinct, specific homo-dimerization patterns. Our results show that this reweighting scheme is effective in assigning structural features known a priori to subfamilies, even when sequence data is relatively scarce. Furthermore, sequence reweighting allows assessing if individual structural contacts pertain to specific subfamilies and it thus paves the way for the identification specificity-determining contacts from sequence variation data.
Subfields: Molecular Biology
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In Molecular Biology
- Lucy J. Colwell
- Sergey Ovchinnikov
- Dorothee Kern
- Hannah K. Wayment-Steele
- W. Pitsawong
- Renee Otten
- Marc Hoemberger
- Julia M Apitz
Citations in the corpus
- Predicting multiple conformations via sequence clustering and AlphaFold2 (2023, positive): “As previous studies have identified evolutionary couplings corresponding to multiple states of domain-based conformational changes 15,16,20 , we speculate that clustering-based MSA preprocessing methods will offer improvements over existing methods 14 and, importantly, insights into the evolution…”
- Prediction of multiple conformational states by combining sequence clustering with AlphaFold2 (2022, methodology): “However, simply subdividing a MSA and making predictions for portions of the MSA has also been used to detect variations in coevolutionary signal within a protein family 24,27,28 .”