Direct Coupling Analysis (DCA) is a statistical inference framework used to infer direct co-evolutionary couplings among residue pairs in multiple sequence alignments. A recent formulation of DCA termed mean field DCA (mfDCA), provides the computational power to apply this tool in a high throughput manner to a number of protein and domain families. mfDCA is able to uncover a large number of native intra-domain and inter-domain residue-residue contacts in many domain families.
An example of a contact map for the bovine pancreatic trypsin inhibitor (PDB ID: 5pti) created with the top 80 DCA coupled pairs (lower triangular) compared to the native c-alpha contacts (upper triangular). The colorbar gradient corresponds to the DI rank with the extremes being the background (white) and the native contacts (blue). The figure was created with the Matlab script plotDCAmap.m. (Right) The top 30 DCA contacts depicted as green sticks in the trypsin inhibitor (PDB ID: 5pti). This figure was generated using Chimera with input files generated by the bash script GeneratePseudobonds.bash.
The predictive performance statistics of mfDCA for 131 domain families and 856 PDB structures is shown in the following figure:
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