Evolutionary Trace for Prediction and Redesign of Protein Functional Sites

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Methods in Molecular Biology (Impact Factor: 1.29). 01/2012; 819:29-42. DOI: 10.1007/978-1-61779-465-0_3
Source: PubMed


The evolutionary trace (ET) is the single most validated approach to identify protein functional determinants and to target mutational analysis, protein engineering and drug design to the most relevant sites of a protein. It applies to the entire proteome; its predictions come with a reliability score; and its results typically reach significance in most protein families with 20 or more sequence homologs. In order to identify functional hot spots, ET scans a multiple sequence alignment for residue variations that correlate with major evolutionary divergences. In case studies this enables the selective separation, recoding, or mimicry of functional sites and, on a large scale, this enables specific function predictions based on motifs built from select ET-identified residues. ET is therefore an accurate, scalable and efficient method to identify the molecular determinants of protein function and to direct their rational perturbation for therapeutic purposes. Public ET servers are located at:

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Available from: Angela D Wilkins, Mar 26, 2014
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    • "c i ranges between 0 and 1, where lower values imply higher evolutionary importance. It is taken from the coverage column of the corresponding ET file, produced by a sequence analysis on homologous proteins(Wilkins et al., 2012). k is -1 if c i is less than the threshold defined as below; otherwise it is 1. "
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    Journal of computational biology: a journal of computational molecular cell biology 09/2015; 22(9):892-904. DOI:10.1089/cmb.2015.0114 · 1.74 Impact Factor
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    • "First, the structures reveal the exposed surface residues that are available for interaction. Second, the protein surfaces may be inspected for signs of binding sites, such as clusters of evolutionarily important residues (Madabushi et al., 2002; Yao et al., 2003; Wilkins et al., 2012). Third, the proposed interacting surfaces can be tested for shape (geometric, steric) and physicochemical (e.g. "
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    • "), one of the most validated approaches currently available for identifying functional sites within a protein (Wilkens et al., 2012). The ET method identifies functionally important amino acid residues by analyzing evolutionary patterns of sequence variations and then ranking every residue by relative importance. "
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