HHblits is the first iterative method based on the pairwise comparison of profile Hidden Markov Models. In benchmarks it achieves better runtimes than other iterative sequence search methods such as PSI-BLAST or HMMER3 by using a fast prefilter based on profile-profile comparison. Furthermore, HHblits greatly improves upon PSI-BLAST and HMMER3 in terms of sensitivity/selectivity and alignment quality.
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HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment.
Remmert M, Biegert A, Hauser A, Söding J.
Nat Methods. 2011 Dec 25;9(2):173-5. doi: 10.1038/nmeth.1818.