Measuring physical residue covariation between two columns of sequence alignment
When two residues in a sequence alignment are suspect for forming a physical interaction, and the protein structure is not available, one could use physical covariation module to evaluate this possibility.
Possible partners of residue 717:
These scores were generated from multiple sequence alignment alone. For this particular example, crystal structure of the protein sequence No. 42 is available and it is possible to verify the analysis. True 3D partners of residue 717 (green color shows correct predictions):
(for positions 708, 711 and 719 the scores were still very positive but far enough from the top to not result in useful predictions: 3.275645, 3.724355, 2.50629)Co-variation analysis thus found 2 out of 5 proximal residues of position 717 placing them in top 4% of all 70 residues scanned, and correctly ruled out several positions that are not spatially close to 717. All without knowing anything about the PDB structure.