ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules

By Haim Ashkenazy, Shiran Abadi, Eric Martz, Ofer Chay, Itay Mayrose, Tal Pupko, Nir Ben-Tal. Nucleic Acids Res., 2016

2,910 citations recorded by the source corpus.

The degree of evolutionary conservation of an amino acid in a protein or a nucleic acid in DNA/RNA reflects a balance between its natural tendency to mutate and the overall need to retain the structural integrity and function of the macromolecule. The ConSurf web server (http://consurf.tau.ac.il), established over 15 years ago, analyses the evolutionary pattern of the amino/nucleic acids of the macromolecule to reveal regions that are important for structure and/or function. Starting from a query sequence or structure, the server automatically collects homologues, infers their multiple sequence alignment and reconstructs a phylogenetic tree that reflects their evolutionary relations. These data are then used, within a probabilistic framework, to estimate the evolutionary rates of each sequence position. Here we introduce several new features into ConSurf, including automatic selection of the best evolutionary model used to infer the rates, the ability to homology-model query proteins, prediction of the secondary structure of query RNA molecules from sequence, the ability to view the biological assembly of a query (in addition to the single chain), mapping of the conservation grades onto 2D RNA models and an advanced view of the phylogenetic tree that enables interactively rerunning ConSurf with the taxa of a sub-tree.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cf1137533c67875b456024130abc9b6f252cf0ec

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In Molecular Biology

1. Richard A. Young
2. Tong Ihn Lee
3. Jérôme Tubiana
4. N. Hannett
5. Maoguang Zhang
6. R. Yan
7. Rémi Monasson
8. A. Ward

Citations in the corpus

• Learning protein constitutive motifs from sequence data (2018, methodology): “This may be explained by the facts that (i) many of the Kunitz domains analyzed are present in two or more copies, and as such, are not all required to strongly bind trypsin Bajaj et al. (2001) and (ii) Kunitz domain may have other specificities encoded by other hidden units.”
• Novel fold of rotavirus glycan-binding domain predicted by AlphaFold2 and determined by X-ray crystallography (2022, methodology): “Evolutionary conservation analysis using the ConSurf server 39 shows that VP8 * B is the most variable domain within VP4 (Supplementary Fig.”
• Transcription factors interact with RNA to regulate genes (2022, methodology): “Evolutionary conservation of TF-ARMs Evolutionary conservation of human TFs was assessed using the ConSurf online server (Ashkenazy et al., 2016).”
• Structural Predictions of the SNX-RGS Proteins Suggest They Belong to a New Class of Lipid Transfer Proteins (2021, positive): “Sequence conservation was mapped onto the modelled SNX27 FERM domain structure with Consurf 55.”
• Structural model of PORCN illuminates disease-associated variants and drug binding sites (2021, positive): “Residues critical for the function of a protein tend to be conserved, and indeed, mapping sequence conservation determined with ConSurf (Ashkenazy et al., 2016) onto the structure of PORCN showed clustering of highly conserved residues in both the catalytic core and the presumed Wnt and PAM-CoA bind”
• A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia (2022, methodology): “Visualize evolutionary conservation was performed by the ConSurf server [22].”
• Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen (2017, methodology): “On the right, S2 is shown as a molecular surface and colored according to sequence conservation as determined by the ConSurf server using 66 diverse coronavirus sequences (85).”