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The Yosshi can help to understand the role of S\u2013S bonds by comparing sequences and structures of homologs with diverse properties and different disulfide connectivity patterns within a common structural fold of a superfamily, and assist to select the most promising hot-spots to improve stability of proteins\/enzymes or modulate their functions by introducing naturally occurring crosslinks. The bioinformatic analysis is supported by the integrated Mustguseal web-server to construct large structure-guided sequence alignments of functionally diverse protein families that can include thousands of proteins based on all available information in public databases. The Yosshi+Mustguseal is a new integrated web-tool for a systematic homology-driven analysis and engineering of S\u2013S bonds that facilitates a broader interpretation of disulfides not just as a factor of structural stability, but rather as a mechanism to implement functional diversity within a superfamily. The results can be downloaded as a content-rich PyMol session file or further studied online using the HTML5-based interactive analysis tools. Both web-servers are free and open to all users at https:\/\/biokinet.belozersky.msu.ru\/yosshi and there is no login requirement.<\/jats:p>","DOI":"10.1093\/nar\/gkz385","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T11:08:20Z","timestamp":1556708900000},"page":"W308-W314","source":"Crossref","is-referenced-by-count":28,"title":["Yosshi: a web-server for disulfide engineering by bioinformatic analysis of diverse protein families"],"prefix":"10.1093","volume":"47","author":[{"given":"Dmitry","family":"Suplatov","sequence":"first","affiliation":[{"name":"Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology and Faculty of Bioengineering and Bioinformatics, Vorobjev hills 1\u201373, Moscow 119991, Russia"}]},{"given":"Daria","family":"Timonina","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology and Faculty of Bioengineering and Bioinformatics, Vorobjev hills 1\u201373, Moscow 119991, Russia"}]},{"given":"Yana","family":"Sharapova","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology and Faculty of Bioengineering and Bioinformatics, Vorobjev hills 1\u201373, Moscow 119991, Russia"}]},{"given":"Vytas","family":"\u0160vedas","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology and Faculty of Bioengineering and Bioinformatics, Vorobjev hills 1\u201373, Moscow 119991, Russia"}]}],"member":"286","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"2019062808223491000_B1","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1074\/jbc.REV118.005604","article-title":"Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation","volume":"294","author":"Chiu","year":"2019","journal-title":"J. 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