Expresso: automatic incorporation of structural information in multiple sequence alignments using 3D-Coffee

Abstract

Expresso is a multiple sequence alignment server that aligns sequences using structural information. The user only needs to provide sequences. The server runs BLAST to identify close homologues of the sequences within the PDB database. These PDB structures are used as templates to guide the alignment of the original sequences using structure-based sequence alignment methods like SAP or Fugue. The final result is a multiple sequence alignment of the original sequences based on the structural information of the templates. An advanced mode makes it possible to either upload private structures or specify which PDB templates should be used to model each sequence. Providing the suitable structural information is available, Expresso delivers sequence alignments with accuracy comparable with structure-based alignments. The server is available on http://www.tcoffee.org/.

Figure 1

Computation of a template-based library. Structural templates are assigned to each original source sequence and these templates are used to generate a structure-based sequence alignment. The final library alignment is generated by aligning each source sequence with its template, thus generating a template-based alignment of the two sources.

Figure 2

Computation of an Expresso Alignment. (a) Default T-Coffee alignment of the thioredoxin HOMSTRAD dataset. Red portions have a high reliability and are expected to be more accurate that the rest. Blue and green portions are the less consistent. Consistency is estimated from a sequence-based T-Coffee library. In this MSA 15% of the columns are similar to the reference HOMSTRAD MSA. (b) Expresso Alignment. Consistency is now estimated from a library computed using template-based alignments. In this alignment 49% of the columns are similar to the HOMSTRAD reference MSA. (c) Automatic template assignment.