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

ABSTRACT 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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    • "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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