Dali server: conservation mapping in 3D

Abstract

Our web site (http://ekhidna.biocenter.helsinki.fi/dali_server) runs the Dali program for protein structure comparison. The web site consists of three parts: (i) the Dali server compares newly solved structures against structures in the Protein Data Bank (PDB), (ii) the Dali database allows browsing precomputed structural neighbourhoods and (iii) the pairwise comparison generates suboptimal alignments for a pair of structures. Each part has its own query form and a common format for the results page. The inputs are either PDB identifiers or novel structures uploaded by the user. The results pages are hyperlinked to aid interactive analysis. The web interface is simple and easy to use. The key purpose of interactive analysis is to check whether conserved residues line up in multiple structural alignments and how conserved residues and ligands cluster together in multiple structure superimpositions. In favourable cases, protein structure comparison can lead to evolutionary discoveries not detected by sequence analysis.

Figure 1.

The walking strategy focuses the search for structural neighbours to the neighbourhood of similar structures found so far. A sparse network of alignments within PDB is stored in an internal database. Once query Q is aligned to some PDB structure(s), a complete set of similar structures can be collected by walking, provided that the network is connected and similarity is approximately transitive.

Figure 2.

Benchmarking the walking strategy. The plots show the distribution of AUC values for single-domain queries in scop 1.75. AUC, where coverage is TP/T and reliability is TP/P with T the number of members of a scop class, P number of matches above a given Z-score, and TP the number of members of a scop class above a given Z-score. Evaluated classes are scop folds (thin line), scop superfamilies (medium thick line) and scop families (thick line). Classes with fewer than 10 or more than 500 members are excluded. Query structures consisted of single domains from scop classes a-d, filtered at 90% sequence identity. Matches to all PDB structures which contained an instance of a domain in scop classes a-d were included in the evaluation.

Figure 3.

Using 3kk7A as query, the Dali server produces several views of the result, including: match list (top left), sequence view (top right), secondary structure view (bottom right), mapping of structural conservation (bottom left) and mapping of sequence conservation (middle bottom). The match list is sorted by Z-scores. The sequence view uses colour for amino acids which have a frequency above 0.5 in a column. The secondary structure view displays the alignment of helices (H), strands (E) and loops (L) as defined by DSSP. Sequence and structural conservation is computed within the selected subset of matches; red positions are maximally conserved and blue positions are not conserved.