The HHpred interactive server for protein homology detection and structure prediction

Abstract

HHpred is a fast server for remote protein homology detection and structure prediction and is the first to implement pairwise comparison of profile hidden Markov models (HMMs). It allows to search a wide choice of databases, such as the PDB, SCOP, Pfam, SMART, COGs and CDD. It accepts a single query sequence or a multiple alignment as input. Within only a few minutes it returns the search results in a user-friendly format similar to that of PSI-BLAST. Search options include local or global alignment and scoring secondary structure similarity. HHpred can produce pairwise query-template alignments, multiple alignments of the query with a set of templates selected from the search results, as well as 3D structural models that are calculated by the MODELLER software from these alignments. A detailed help facility is available. As a demonstration, we analyze the sequence of SpoVT, a transcriptional regulator from Bacillus subtilis. HHpred can be accessed at http://protevo.eb.tuebingen.mpg.de/hhpred.

Figure 1

Start page for the HHpred server at with part of a help window overlaid.

Figure 2

Search results for SpoVT from Bacillus subtilis. The summary hit list at the top shows that SpoVT consists of two domains: the N-terminal domain is very similar to AbrB (rank 1) and clearly homologous to MazE (rank 3) and the C-terminal domain is similar to GAF and PAS domains (rank 2, 4–9). In the summary hit list, column ‘Prob’ gives the probability that the hit is homologous to the query. This is the principle measure of statistical significance. In the alignments below, the sequences marked ‘Q’ (‘T’) refer to the query (template) alignment. Sequences ‘ss_pred’ and ‘ss_conf’ denote the PSI-PRED secondary structure prediction and confidence values, ‘ss_dssp’ is the secondary strcuture assigned by DSSP. Upper an lower case amino acids in the consensus sequences indicate high (≳60%) and moderate (≳40%) conservation, respectively. Symbols indicating the quality of the column–column match: ‘|’ very good, ‘+’ good, ‘·’ neutral, ‘−’ bad and ‘=’ very bad.