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

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

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  • 1Gene Center and Center for Integrated Protein Science Munich, Ludwig-Maximilians Universität München, Munich, Germany.


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; 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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