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. Specifi cally, 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.
CITATION STYLE
Morcos, F., Hwa, T., Onuchic, J. N., & Weigt, M. (2014). Direct coupling analysis for protein contact prediction. Methods in Molecular Biology, 1137, 55–70. https://doi.org/10.1007/978-1-4939-0366-5_5
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