{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:45:42Z","timestamp":1773272742699,"version":"3.50.1"},"reference-count":38,"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><jats:p>Motivation: The observed correlations between pairs of homologous protein sequences are typically explained in terms of a Markovian dynamic of amino acid substitution. This model assumes that every location on the protein sequence has the same background distribution of amino acids, an assumption that is incompatible with the observed heterogeneity of protein amino acid profiles and with the success of profile multiple sequence alignment.<\/jats:p><jats:p>Results: We propose an alternative model of amino acid replacement during protein evolution based upon the assumption that the variation of the amino acid background distribution from one residue to the next is sufficient to explain the observed sequence correlations of homologs. The resulting dynamical model of independent replacements drawn from heterogeneous backgrounds is simple and consistent, and provides a unified homology match score for sequence\u2013sequence, sequence\u2013profile and profile\u2013profile alignment.<\/jats:p><jats:p>Contact: \u00a0gec@compbio.berkeley.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti109","type":"journal-article","created":{"date-parts":[[2004,11,6]],"date-time":"2004-11-06T01:14:14Z","timestamp":1099703654000},"page":"975-980","source":"Crossref","is-referenced-by-count":17,"title":["An alternative model of amino acid replacement"],"prefix":"10.1093","volume":"21","author":[{"given":"Gavin E.","family":"Crooks","sequence":"first","affiliation":[{"name":"Department of Plant and Microbial Biology 111 Koshland Hall #3102 University of California Berkeley, CA 94720-3102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology 111 Koshland Hall #3102 University of California Berkeley, CA 94720-3102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,11,5]]},"reference":[{"key":"2023013107270782600_B1","unstructured":"Altschul, S.F. 1991Amino acid substitution matrices from an information theoretic perspective. J. Mol. Biol.219555\u2013565"},{"key":"2023013107270782600_B2","doi-asserted-by":"crossref","unstructured":"Altschul, S.F. 1993A protein alignment scoring system sensitive at all evolutionary distances. J. Mol. Evol.36290\u2013300","DOI":"10.1007\/BF00160485"},{"key":"2023013107270782600_B3","unstructured":"Benner, S.A., Cohen, M.A., Gonnet, G.H. 1994Amino acid substitution during functionally constrained divergent evolution of protein sequences. Protein Eng.71323\u20131332"},{"key":"2023013107270782600_B4","doi-asserted-by":"crossref","unstructured":"Brenner, S.E., Chothia, C., Hubbard, T.J.P. 1998Assessing sequence comparison methods with reliable structurally identified distant evolutionary relationships. Proc. Natl Acad. Sci. USA956073\u20136078","DOI":"10.1073\/pnas.95.11.6073"},{"key":"2023013107270782600_B5","unstructured":"Brenner, S.E., Koehl, P., Levitt, M. 2000The ASTRAL compendium for protein structure and sequence analysis. 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