CSA: comprehensive comparison of pairwise protein structure alignments

Abstract

CSA is a web server for the computation, evaluation and comprehensive comparison of pairwise protein structure alignments. Its exact alignment engine computes either optimal, top-scoring alignments or heuristic alignments with quality guarantee for the inter-residue distance-based scorings of contact map overlap, PAUL, DALI and MATRAS. These and additional, uploaded alignments are compared using a number of quality measures and intuitive visualizations. CSA brings new insight into the structural relationship of the protein pairs under investigation and is a valuable tool for studying structural similarities. It is available at http://csa.project.cwi.nl.

Figure 1.

CSA website with different tabs and parts of the information displayed for the cmo alignment of 1otrA and 2di0A.

Figure 2.

A radar chart for comparison of alignment scores for six different alignments of 1otrA and 2di0A. The closer a point is to 1, the better the corresponding score. cmo, paul, dalix and matrasx alignments have been computed by our exact algorithm and are provably optimal concerning their respective score. The SISY reference alignment aligns 38 residues of the CUE2 domain. The dali alignment was computed by the dali server and has slightly lower dali score than the optimal dalix alignment. The reference alignment is far behind in all scores except RMSD100 and TM-score, for which it performs quite well. The matrasx alignment performs especially poor for these two measures. Intuitively, the dalix alignment is most preferable since it has optimal dali and close to optimal cmo, paul and matras scores, as well as the best TM-score and RMSD100.

Figure 3.

(A) The two calmodulin conformers (PDB IDs 4cln and 2bbm) superpositioned according to the TM-alignment, which aligns only one of the two regions that move relative to each other. (B) Comparison of the alignment traces. Each axis corresponds to one conformer. Black boxes denote residue pairs aligned by all three scorings, paul, tm-align and dast. Light (intermediate) shades of gray denotes residue pairs aligned by only one (two) scorings. paul aligns all residues of the two conformers, tmalign and dast the C-terminal region. (C) The radar chart illustrates the difference between scorings that are more in favor of a flexible alignment (cmo, paul, dali and matras) and scorings that are more in favor of a rigid superposition of low RMSD. (D) Distance difference matrices show the difference between the flexible paul alignment, that aligns all residues in spite of large distance differences (colored blue), and the TM- and dast alignment that only align the C-terminal region.