ConSurf 2016: an Improved Methodology to Estimate and Visualize Evolutionary Conservation in Macromolecules

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 May 12

PMID 27166375

Citations 1476

Authors

Haim Ashkenazy

Shiran Abadi

Eric Martz

Ofer Chay

Itay Mayrose

Tal Pupko

Nir Ben-Tal

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Improvement in the Thermal Stability of MHETase by Sequence and Structure-Guided Calculation.

Duan S, Chao T, Wu Y, Wei Z, Cao S Molecules. 2025; 30(5).

PMID: 40076213 PMC: 11902034. DOI: 10.3390/molecules30050988.

Discovery of mono-ADP ribosylating toxins with high structural homology to Pseudomonas exotoxin A.

Masuyer G, Taverner A, MacKay J, Lima Marques A, Wang Y, Hunter T Commun Biol. 2025; 8(1):413.

PMID: 40069285 PMC: 11897225. DOI: 10.1038/s42003-025-07845-y.

Crystal structures of monomeric BsmI restriction endonuclease reveal coordinated sequential cleavage of two DNA strands.

Sieskind R, Missoury S, Madru C, Commenge I, Niogret G, Hollenstein M Commun Biol. 2025; 8(1):387.

PMID: 40055548 PMC: 11889245. DOI: 10.1038/s42003-025-07612-z.

PyPropel: a Python-based tool for efficiently processing and characterising protein data.

Sun J, Ru J, Cribbs A, Xiong D BMC Bioinformatics. 2025; 26(1):70.

PMID: 40025421 PMC: 11871610. DOI: 10.1186/s12859-025-06079-3.

Genomic diversity of mcr-carrying plasmids and the role of type IV secretion systems in IncI2 plasmids conjugation.

Li Z, Li Z, Peng Y, Zhang M, Wen Y, Lu X Commun Biol. 2025; 8(1):342.

PMID: 40025288 PMC: 11873049. DOI: 10.1038/s42003-025-07748-y.

References

Veidenberg A, Medlar A, Loytynoja A . Wasabi: An Integrated Platform for Evolutionary Sequence Analysis and Data Visualization. Mol Biol Evol. 2015; 33(4):1126-30. DOI: 10.1093/molbev/msv333. View

Huang Y, Golding G . Phylogenetic Gaussian process model for the inference of functionally important regions in protein tertiary structures. PLoS Comput Biol. 2014; 10(1):e1003429. PMC: 3894161. DOI: 10.1371/journal.pcbi.1003429. View

Lichtarge O, Bourne H, Cohen F . Evolutionarily conserved Galphabetagamma binding surfaces support a model of the G protein-receptor complex. Proc Natl Acad Sci U S A. 1996; 93(15):7507-11. PMC: 38775. DOI: 10.1073/pnas.93.15.7507. View

Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T . ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 2005; 33(Web Server issue):W299-302. PMC: 1160131. DOI: 10.1093/nar/gki370. View

Tamura K . Estimation of the number of nucleotide substitutions when there are strong transition-transversion and G+C-content biases. Mol Biol Evol. 1992; 9(4):678-87. DOI: 10.1093/oxfordjournals.molbev.a040752. View

Remmert M, Biegert A, Hauser A, Soding J . HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat Methods. 2011; 9(2):173-5. DOI: 10.1038/nmeth.1818. View

Mulligan C, Fenollar-Ferrer C, Fitzgerald G, Vergara-Jaque A, Kaufmann D, Li Y . The bacterial dicarboxylate transporter VcINDY uses a two-domain elevator-type mechanism. Nat Struct Mol Biol. 2016; 23(3):256-63. PMC: 5215794. DOI: 10.1038/nsmb.3166. View

Nawrocki E, Burge S, Bateman A, Daub J, Eberhardt R, Eddy S . Rfam 12.0: updates to the RNA families database. Nucleic Acids Res. 2014; 43(Database issue):D130-7. PMC: 4383904. DOI: 10.1093/nar/gku1063. View

Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View

10.

Biegert A, Soding J . Sequence context-specific profiles for homology searching. Proc Natl Acad Sci U S A. 2009; 106(10):3770-5. PMC: 2645910. DOI: 10.1073/pnas.0810767106. View

11.

Fu L, Niu B, Zhu Z, Wu S, Li W . CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics. 2012; 28(23):3150-2. PMC: 3516142. DOI: 10.1093/bioinformatics/bts565. View

12.

Katoh K, Standley D . MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013; 30(4):772-80. PMC: 3603318. DOI: 10.1093/molbev/mst010. View

13.

Pupko T, Bell R, Mayrose I, Glaser F, Ben-Tal N . Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues. Bioinformatics. 2002; 18 Suppl 1:S71-7. DOI: 10.1093/bioinformatics/18.suppl_1.s71. View

14.

Whelan S, Goldman N . A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol. 2001; 18(5):691-9. DOI: 10.1093/oxfordjournals.molbev.a003851. View

15.

Rost B . Twilight zone of protein sequence alignments. Protein Eng. 1999; 12(2):85-94. DOI: 10.1093/protein/12.2.85. View

16.

Guy M, Young D, Payea M, Zhang X, Kon Y, Dean K . Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis. Genes Dev. 2014; 28(15):1721-32. PMC: 4117946. DOI: 10.1101/gad.245936.114. View

17.

Toporik A, Borukhov I, Apatoff A, Gerber D, Kliger Y . Computational identification of natural peptides based on analysis of molecular evolution. Bioinformatics. 2014; 30(15):2137-41. DOI: 10.1093/bioinformatics/btu195. View

18.

Wong T, Roccatano D, Schwaneberg U . Steering directed protein evolution: strategies to manage combinatorial complexity of mutant libraries. Environ Microbiol. 2007; 9(11):2645-59. DOI: 10.1111/j.1462-2920.2007.01411.x. View

19.

Lichtarge O, Yamamoto K, Cohen F . Identification of functional surfaces of the zinc binding domains of intracellular receptors. J Mol Biol. 1998; 274(3):325-37. DOI: 10.1006/jmbi.1997.1395. View

20.

Lorenz R, Bernhart S, Honer Zu Siederdissen C, Tafer H, Flamm C, Stadler P . ViennaRNA Package 2.0. Algorithms Mol Biol. 2011; 6:26. PMC: 3319429. DOI: 10.1186/1748-7188-6-26. View