{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:26:58Z","timestamp":1758709618697,"version":"3.32.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC0901704","2017YFA0505500"],"award-info":[{"award-number":["2016YFC0901704","2017YFA0505500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012164","name":"National High-tech Research and Development Program","doi-asserted-by":"publisher","award":["2015AA020105"],"award-info":[{"award-number":["2015AA020105"]}],"id":[{"id":"10.13039\/501100012164","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21377085","31770070"],"award-info":[{"award-number":["21377085","31770070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Quant. Biol."],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Arsenic has a broad anti\u2010cancer ability against hematologic malignancies and solid tumors. To systematically understand the biological functions of arsenic, we need to identify arsenic\u2010binding proteins in human cells. However, due to lack of effective theoretical tools and experimental methods, only a few arsenic\u2010binding proteins have been identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on the crystal structure of ArsM, we generated a single mutation free energy profile for arsenic binding using free energy perturbation methods. Multiple validations provide an indication that our computational model has the ability to predict arsenic\u2010binding proteins with desirable accuracy. We subsequently apply this computational model to scan the entire human genome to identify all the potential arsenic\u2010binding proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The computationally predicted arsenic\u2010binding proteins show a wide range of biological functions, especially in the signaling transduction pathways. In the signaling transduction pathways, arsenic directly binds to the key factors ( <jats:italic>e.g<\/jats:italic>., Notch receptors, Notch ligands, Wnt family proteins, TGF\u2010beta, and their interacting proteins) and results in significant inhibitions on their enzymatic activities, further having a crucial impact on the related signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Arsenic has a significant impact on signaling transduction in cells. Arsenic binding to proteins can lead to dysfunctions of the target proteins, having crucial impacts on both signaling pathway and gene transcription. We hope that the computationally predicted arsenic\u2010binding proteins and the functional analysis can provide a novel insight into the biological functions of arsenic, revealing a mechanism for the broad anti\u2010cancer of arsenic.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s40484-019-0169-6","type":"journal-article","created":{"date-parts":[[2019,4,27]],"date-time":"2019-04-27T06:55:37Z","timestamp":1556348137000},"page":"182-189","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Computational prediction and functional analysis of arsenic\u2010binding proteins in human cells"],"prefix":"10.1002","volume":"7","author":[{"given":"Shichao","family":"Pang","sequence":"first","affiliation":[{"name":"<!--1--> Department of Statistics School of Mathematical Sciences Shanghai Jiao Tong University Shanghai 200240 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junchen","family":"Yang","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Bioinformatics and Biostatistics College of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilei","family":"Zhao","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Bioinformatics and Biostatistics College of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixue","family":"Li","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Bioinformatics and Biostatistics College of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China"},{"name":"<!--3--> Key Laboratory of Computational Biology CAS\u2010MPG Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingfang","family":"Wang","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Bioinformatics and Biostatistics College of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China"},{"name":"<!--4--> Key Laboratory of Systems Biomedicine (Ministry of Education) Shanghai Center for Systems Biomedicine Shanghai Jiao Tong University Shanghai 200240 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August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors Shichao Pang, Junchen Yang, Yilei Zhao, Yixue Li and Jingfang Wang declare that they have no conflict of interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethics Guidelines"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethics 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