hh-suite

name	hh-suite
description	HH-suite3 (HHblits / HHsearch) — remote protein homology via HMM–HMM alignment (Söding lab). Use when: (1) Sequence identity is too low for BLAST/MMseqs easy hits, (2) Building/searching profile HMMs (BFD, UniClust, Pfam-style DBs), (3) Feeding sensitive MSAs into structure prediction Upstream: https://github.com/soedinglab/hh-suite. Route via homology-search; complements mmseqs2 and foldseek.
license	MIT
category	analysis-tools
tags	["HHblits","HHsearch","HH-suite","HMM","remote-homology","search"]
upstream	https://github.com/soedinglab/hh-suite
stage	function

HH-suite3

Upstream: soedinglab/hh-suite

Citation

Remmert, M., Biegert, A., Hauser, A. & Söding, J. HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat. Methods 9, 173–175 (2012). https://doi.org/10.1038/nmeth.1818

See also docs/references.md.

Analytical thinking

Profile–profile search (HMM–HMM) recovers remote homologs that single-sequence tools miss. Still a sequence/profile method — pair with foldseek when structures exist. Large DBs (BFD via PLASS catalogues, UniClust) need disk and careful pinning.

vs	Prefer HH-suite when
mmseqs2	Need iterative profile search / MSA for folding
foldseek	No structures yet; profile MSA / remote homology
plmsearch	Classical HMM profiles preferred over PLM embeddings

How to run

# single HHblits iteration against a prepared HH-suite DB
hhblits -i query.faa -o temp/hh/query.hhr -oa3m temp/hh/query.a3m \
  -n 1 -d /path/to/hh_database
# HHsearch: query HMM/a3m against HMM DB — see upstream docs

Decision tree

Remote homology without structure?
├─ Profile HMM iterative search → hh-suite (hhblits)
├─ Fast catalogue AA search → mmseqs2
├─ Structure / 3Di → foldseek
└─ Vector DB → erast

Related skills

homology-search · mmseqs2 · foldseek · plass · plmsearch · tool-selection