Cited by 2,288Genomics and Phylogenetic StudiesMachine Learning in BioinformaticsProtein Structure and Dynamics

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

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Remmert, Michael, Biegert, Andreas, Hauser, Andreas, Söding, Johannes·2012·Nature Methods

Abstract

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.

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  • The availability of predicted structures may help identify meaningful evolutionary relationships.

    “Although some advanced sequence-based methods can already assist in this task39–41, the availability of predicted structures may help identify meaningful evolutionary relationships.”

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Research works printed but not linked: 4

  1. Biegert, A. & Söding, J. Proc. Natl. Acad. Sci. USA 106, 3770-3775 (2009).
  2. Gonzalez, M.W. & Pearson, W.R. Nucleic Acids Res. 38, 2177-2189 (2010).
  3. Aydin, Z., Singh, A., Bilmes, J. & Noble, W. BMC Bioinformatics 12, 154 (2011).
  4. Marks, D.S. et al. PLoS ONE 6, e28766 (2011).

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Authors
Remmert, M., Biegert, A., Hauser, A., & Söding, J.
Affiliations
  • Center for Integrated Protein Science Munich (DE)
  • Max Planck Society (DE)
Corresponding author
Söding, Johannes
Venue
Nature Methods
Published
2011-12-25
Volume
9
Issue
2
Pages
173-175
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
OpenAlex
W2051210555
Cited by
2,288
References
24
Citations by year
2026: 110 · 2025: 178 · 2024: 202 · 2023: 213 · 2022: 209 · 2021: 231 · 2020: 211 · 2019: 211 · 2018: 151 · 2017: 148 · 2016: 144 · 2015: 117 · 2014: 72 · 2013: 62 · 2012: 25
FWCI
20.66
Type
journal article
Language
en
Open access
Locations
  • Nature Methods (publishedVersion)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • Max Planck Digital Library (submittedVersion, other-oa)
Funders
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
protein sequence search, profile hidden Markov models, sequence alignment, protein function prediction, protein structure prediction
MeSH terms
Markov Chains, Proteins, Sequence Alignment

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