DARC (Deep Analysis of Residue Constraints)

DARC performs concurrent identification of residue direct couplings, of protein subgroup-specific patterns, and of correlations between subgroup patterns and structure, between subgroup patterns and direct couplings, and between direct couplings and structure.  To assess biological relevance, DARC provides measures of statistical significance, and visualizes constraints within sequence alignments and within 3D structures.

DARC and sbsmpl_dca executables.  Extract the executables by first typing “gunzip darc1.0.6_i86linux64.tar.gz” and then “tar xvf darc_i86linux641.0.6.tar”.  Go into the darc1.0.6_i86linux64 directory and follow the instructions in the readme file.

Input files needed to reproduce the bacterial DNA clamp loader DARC analyses described in Tondnevis, Dudenhausen, Miller, McKenna, Altschul, Bloom & Neuwald. 2019. Deep Analysis of Residue Constraints (DARC): identifying determinants of protein functional specificity. Scientific Reports (revision under review).

A pdf file with additional information.

DARC and sbsmpl_dca C++ source code 

sbsmpl_dca assesses the robustness of direct coupling analysis (DCA) through subsampling.  It will map the consistently highest scoring DC pairs to a protein 3D structure.  This should be used in conjunction with DARC to reliably identify the most directly coupled residues.

MAPGAPS can generate very large MSAs as input to darc.  MAPGAPS uses a curated hierarchical multiple sequence alignment (MSA) as a query to identify and multiply align related protein sequences within a fasta-formatted database.