eeadcsiccompbio/tfcompare repository overview

⁠tfcompare

This repository distributes a Docker image with tfcompare ready to use. TFcompare is a tool for structural alignment of DNA motifs and protein domains from DNA-binding protein complexes in PDB format. This legacy container replaces the web server at http://floresta.eead.csic.es/tfcompare⁠

The TFcompare algorithm calculates structural alignments between three dimensional structures of two DNA-protein complexes. The most interesting feature of TFcompare when compared with other methods is that it extracts individual protein domains and their recognized DNA sequences, aligning them separately and returning not only the structure superposition but the DNA sequence superposition too. In this way we can compare single domain affinity for different DNA sequences in DNA-protein complexes, especially transcription factors and their recognized cis elements.

Read more at:

A Sebastian, B Contreras-Moreira (2013) The twilight zone of cis element alignments. https://doi.org/10.1093/nar/gks1301⁠

⁠Algorithm

TFcompare takes as input two PDB files. Pfam domains contacting DNA are calculated and trimmed from the original structure. Then all the domains from the first structure are aligned to all the domains from the second in several steps:

• The program MAMMOTH performs the structural alignment.
• The produced transformation matrices are applied to the coordinates of the DNA binding sites in order to derive the equivalent cis element superpositions.
• Root-mean-squared deviations of superposed coordinates are calculated with beta-carbon atoms (proteins) and with N9 (purines) and N1 (pyrimidines) atoms (DNA).
• Structural alignments are scored in terms of
  • i) the number of identical superposed nucleotides (DNA Score 1-0)
  • ii) the sum of N9 and N1 atom pairs within 3.5A (DNA Score).

⁠File formats

Input files are expected to be in PDB format. Should you have other protein-DNA complexes in in other formats you can convert them with other tools such as MAXIT⁠ or CIFTr⁠.

⁠Installing Docker

See instructions here⁠.

⁠Examples of use

Once Docker is set up you can see the options or run the tfcompare demo in the terminal as follows:

docker run --rm -it eeadcsiccompbio/tfcompare tfcompare 

docker run --rm -it eeadcsiccompbio/tfcompare tfcompare -d 

Note: This takes longer the first time as the Docker image first needs to be downloaded.

In order to analyze your own, local files you can do:

cd your_pdb_folder/
docker run --rm -v "$PWD:$PWD" -w "$PWD" -u $UID:$GROUPS -it eeadcsiccompbio/tfcompare tfcompare -q file1.pdb -s file2.pdb

Note: The results will be saved to your local folder.

⁠Output

Results are ordered by structural similarity (RMSD), from both protein domain and DNA. Each row contains an alignment of a pair of DNA binding domains, showing a picture of their structures before and after superposition. DNA alignment is also shown.

Results column headers and their meaning:

Pair: Pair number
Domain_Query: PDB name, chain and domain number of the Query
Domain_Sbjct: PDB name, chain and domain number of the Sbjct
DNA_Query: DNA site recognized by the Query domain
DNA_Sbjct: DNA site recognized by the Query domain
Similar: 1 if both protein domains and DNA sites are below RMSD thresholds, 5.0 A and 3.5 A respectively
DNA_Alignment: DNA sites structurally aligned
DNA_Aligned: Number of aligned nucleotides
DNA_Score_1-0: Number of identical nucleotides
DNA_Score: Structural alignment score
DNA_RMSD: RMSD of the structurally aligned DNA sites
PROT_RMSD: RMSD of the structurally aligned protein domains
3D_Alignment: 3D Visualization of aligned structures