The HHpred interactive server for protein homology detection and structure prediction

HHpred is a fast web server for remote protein homology detection and structure prediction, and the first tool to implement pairwise comparison of profile hidden Markov models. It searches a wide choice of databases including PDB, SCOP, Pfam, SMART, COGs, and CDD, accepts either a single query sequence or a multiple alignment as input, and within minutes returns results in a user-friendly format similar to PSI-BLAST. Search options include local or global alignment and scoring of secondary-structure similarity.

Beyond detection, HHpred produces pairwise query-template alignments, multiple alignments of the query with selected templates, and 3D structural models calculated by the MODELLER software from those alignments. The authors demonstrate its utility by analyzing SpoVT, a transcriptional regulator from Bacillus subtilis. HHpred mattered as an accessible, fast, and accurate resource that brought profile-HMM comparison to a broad community of biologists for homology and structure inference.