ConSurf: Using Evolutionary Data to Raise Testable Hypotheses about Protein Function

Israel Journal of Chemistry - Tập 53 Số 3-4 - Trang 199-206 - 2013
Gershon Celniker1,2,3, Guy Nimrod4,1, Haim Ashkenazy2, Fabian Glaser5, Eric Martz6, Itay Mayrose3, Tal Pupko2, Nir Ben‐Tal1
1The Department of Biochemistry and Molecular Biology, Tel Aviv University, 69978 Tel Aviv (Israel)
2The Department of Cell Research and Immunology, Tel Aviv University, 69978 Tel Aviv (Israel)
3The Department of Molecular Biology and Ecology of Plants, Tel Aviv University, 69978 Tel Aviv (Israel)
4Present address: Biolojic Design, Akiva Aria 25, Tel Aviv 6215425 (Israel)
5Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion – Israel Institute of Technology, Haifa 32000 (Israel)
6Department of Microbiology, University of Massachusetts Amherst, MA, USA.

Tóm tắt

Abstract

Many mutations disappear from the population because they impair protein function and/or stability. Thus, amino acid positions that are essential for proper function evolve more slowly than others, or in other words, the slow evolutionary rate of a position reflects its importance. ConSurf (http://consurf.tau.ac.il), reviewed in this manuscript, exploits this to reveal key amino acid positions that are important for maintaining the native conformation(s) of the protein and its function, be it binding, catalysis, transport, etc. Given the sequence or 3D structure of the query protein as input, a search for similar sequences is conducted and the sequences are aligned. The multiple sequence alignment is subsequently used to calculate the evolutionary rates of each amino acid site, using Bayesian or maximum‐likelihood algorithms. Both algorithms take into account the evolutionary relationships between the sequences, reflected in phylogenetic trees, to alleviate problems due to uneven (biased) sampling in sequence space. This is particularly important when the number of sequences is low. The ConSurf‐DB, a new release of which is presented here, provides precalculated ConSurf conservation analysis of nearly all available structures in the Protein DataBank (PDB). The usefulness of ConSurf for the study of individual proteins and mutations, as well as a range of large‐scale, genome‐wide applications, is reviewed.

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Israel Journal of Chemistry

Tập 53 Số 3-4

199-206

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