Computational Drug Discovery and Design pp 29-42

Part of the Methods in Molecular Biology book series (MIMB, volume 819)

Evolutionary Trace for Prediction and Redesign of Protein Functional Sites

  • Angela Wilkins
  • Serkan Erdin
  • Rhonald Lua
  • Olivier Lichtarge
Protocol

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: http://mammoth.bcm.tmc.edu/.

Key words

Evolutionary trace Protein design Protein engineering Function annotation Phylogenomics Protein–protein interaction 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Angela Wilkins
    • 1
    • 2
  • Serkan Erdin
    • 1
    • 2
  • Rhonald Lua
    • 1
  • Olivier Lichtarge
    • 2
    • 3
  1. 1.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.W. M. Keck Center for Interdisciplinary Bioscience TrainingHoustonUSA
  3. 3.Department of Molecular and Human Genetics, Verna and Marrs Mclean Department of Biochemistry and Molecular BiologyBaylor College of MedicineHoustonUSA

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