{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:13:29Z","timestamp":1787721209354,"version":"build-2784847793"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: Protein homology detection and sequence alignment are at the basis of protein structure prediction, function prediction and evolution.<\/jats:p>\n                  <jats:p>Results: We have generalized the alignment of protein sequences with a profile hidden Markov model (HMM) to the case of pairwise alignment of profile HMMs. We present a method for detecting distant homologous relationships between proteins based on this approach. The method (HHsearch) is benchmarked together with BLAST, PSI-BLAST, HMMER and the profile\u2013profile comparison tools PROF_SIM and COMPASS, in an all-against-all comparison of a database of 3691 protein domains from SCOP 1.63 with pairwise sequence identities below 20%.<\/jats:p>\n                  <jats:p>Sensitivity: When the predicted secondary structure is included in the HMMs, HHsearch is able to detect between 2.7 and 4.2 times more homologs than PSI-BLAST or HMMER and between 1.44 and 1.9 times more than COMPASS or PROF_SIM for a rate of false positives of 10%. Approximately half of the improvement over the profile\u2013profile comparison methods is attributable to the use of profile HMMs in place of simple profiles.<\/jats:p>\n                  <jats:p>Alignment quality: Higher sensitivity is mirrored by an increased alignment quality. HHsearch produced 1.2, 1.7 and 3.3 times more good alignments (\u2018balanced\u2019 score &amp;gt;0.3) than the next best method (COMPASS), and 1.6, 2.9 and 9.4 times more than PSI-BLAST, at the family, superfamily and fold level, respectively.<\/jats:p>\n                  <jats:p>Speed: HHsearch scans a query of 200 residues against 3691 domains in 33 s on an AMD64 2GHz PC. This is 10 times faster than PROF_SIM and 17 times faster than COMPASS.<\/jats:p>\n                  <jats:p>Availability: HHsearch can be downloaded from http:\/\/www.protevo.eb.tuebingen.mpg.de\/download\/ together with up-to-date versions of SCOP and PFAM. A web server is available at http:\/\/www.protevo.eb.tuebingen.mpg.de\/toolkit\/index.php?view=hhpred<\/jats:p>\n                  <jats:p>Contact: \u00a0johannes.soeding@tuebingen.mpg.de<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti125","type":"journal-article","created":{"date-parts":[[2004,11,5]],"date-time":"2004-11-05T20:14:14Z","timestamp":1099685654000},"page":"951-960","source":"Crossref","is-referenced-by-count":2172,"title":["Protein homology detection by HMM\u2013HMM comparison"],"prefix":"10.1093","volume":"21","author":[{"given":"Johannes","family":"S\u00f6ding","sequence":"first","affiliation":[{"name":"Department of Protein Evolution, Max-Planck-Institute for Developmental Biology Spemannstrasse 35, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,11,5]]},"reference":[{"key":"2023013107271078000_B1","doi-asserted-by":"crossref","unstructured":"Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J. 1990Basic local alignment search tool. 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