Protein Structure Prediction pp 55-70

Part of the Methods in Molecular Biology book series (MIMB, volume 1137) | Cite as

Direct Coupling Analysis for Protein Contact Prediction

  • Faruck Morcos
  • Terence Hwa
  • José N. Onuchic
  • Martin Weigt
Protocol

Abstract

During evolution, structure, and function of proteins are remarkably conserved, whereas amino-acid sequences vary strongly between homologous proteins. Structural conservation constrains sequence variability and forces different residues to coevolve, i.e., to show correlated patterns of amino-acid occurrences. However, residue correlation may result from direct coupling, e.g., by a contact in the folded protein, or be induced indirectly via intermediate residues. To use empirically observed correlations for predicting residue–residue contacts, direct and indirect effects have to be disentangled. Here we present mechanistic details on how to achieve this using a methodology called Direct Coupling Analysis (DCA). DCA has been shown to produce highly accurate estimates of amino-acid pairs that have direct reciprocal constraints in evolution. Specifically, we provide instructions and protocols on how to use the algorithmic implementations of DCA starting from data extraction to predicted-contact visualization in contact maps or representative protein structures.

Keywords

Direct coupling analysis Maximum entropy Contact prediction Residue–residue interactions Coevolution Direct correlations Statistical inference 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Faruck Morcos
    • 1
  • Terence Hwa
    • 2
  • José N. Onuchic
    • 1
  • Martin Weigt
    • 3
  1. 1.Center for Theoretical Biological PhysicsRice UniversityHoustonUSA
  2. 2.Center for Theoretical Biological PhysicsUniversity of California at San DiegoLa JollaUSA
  3. 3.UMR7238—Laboratoire de Génomique des MicroorganismesUniversité Pierre et Marie CurieParisFrance

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