HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment

Nat Methods. 2011 Dec 25;9(2):173-5. doi: 10.1038/nmeth.1818.


Sequence-based protein function and structure prediction depends crucially on sequence-search sensitivity and accuracy of the resulting sequence alignments. We present an open-source, general-purpose tool that represents both query and database sequences by profile hidden Markov models (HMMs): 'HMM-HMM-based lightning-fast iterative sequence search' (HHblits; http://toolkit.genzentrum.lmu.de/hhblits/). Compared to the sequence-search tool PSI-BLAST, HHblits is faster owing to its discretized-profile prefilter, has 50-100% higher sensitivity and generates more accurate alignments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Markov Chains
  • Proteins / chemistry*
  • Sequence Alignment*


  • Proteins