{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:39:45Z","timestamp":1760243985809,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2009,5,26]],"date-time":"2009-05-26T00:00:00Z","timestamp":1243296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Algorithms"],"abstract":"<jats:p>Considerable importance in molecular biophysics is attached to influencing by mutagenesis the specific properties of a protein family. The working hypothesis is that mutating residues at few selected positions can affect specificity. Statistical analysis of homologue sequences can identify putative specificity determining positions (SDPs) and help to shed some light on the peculiarities underlying their functional role. In this work, we present an approach to identify such positions inspired by state of the art mutual information-based SDP prediction methods. The algorithm based on this approach provides a systematic procedure to point at the relevant physical characteristics of putative SPDs and can investigate the effects of correlated mutations. The method is tested on two standard benchmarks in the field and further validated in the context of a biologically interesting problem: the multimerization of the Intrinsically Fluorescent Proteins (IFP).<\/jats:p>","DOI":"10.3390\/a2020764","type":"journal-article","created":{"date-parts":[[2009,5,26]],"date-time":"2009-05-26T12:05:05Z","timestamp":1243339505000},"page":"764-789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SDPhound, a Mutual Information-Based Method to Investigate Specificity-Determining Positions"],"prefix":"10.3390","volume":"2","author":[{"given":"Sara","family":"Bonella","sequence":"first","affiliation":[{"name":"NEST Scuola Normale Superiore and CNR-INFM, Piazza dei Cavalieri 7, I-56126 Pisa, Italy"}]},{"given":"Walter","family":"Rocchia","sequence":"additional","affiliation":[{"name":"NEST Scuola Normale Superiore and CNR-INFM, Piazza dei Cavalieri 7, I-56126 Pisa, Italy"},{"name":"Drug Discovery and Development, Italian Institute of Technology, via Morego 30, Genova I-161631, Italy"}]},{"given":"Pietro","family":"Amat","sequence":"additional","affiliation":[{"name":"NEST Scuola Normale Superiore and CNR-INFM, Piazza dei Cavalieri 7, I-56126 Pisa, Italy"}]},{"given":"Riccardo","family":"Nifos\u00ed","sequence":"additional","affiliation":[{"name":"NEST Scuola Normale Superiore and CNR-INFM, Piazza dei Cavalieri 7, I-56126 Pisa, Italy"}]},{"given":"Valentina","family":"Tozzini","sequence":"additional","affiliation":[{"name":"NEST Scuola Normale Superiore and CNR-INFM, Piazza dei Cavalieri 7, I-56126 Pisa, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2009,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/157489306775330633","article-title":"Computational prediction of functionally important regions in proteins","volume":"1","author":"Pazos","year":"2006","journal-title":"Curr. 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