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However, these valuable data are not sufficiently covered by the available databases. In this study, a major update of VARIDT (a database previously constructed to provide DTs\u2019 variability data) was thus described. First, the experimentally resolved structures of all DTs reported in the original VARIDT were discovered from PubMed and Protein Data Bank. Second, the structural variability data of each DT were collected by literature review, which included: (a) mutation-induced spatial variations in folded state, (b) difference among DT structures of human and model organisms, (c) outward\/inward-facing DT conformations and (d)\u00a0xenobiotics-driven alterations in the 3D complexes. Third, for those DTs without experimentally resolved structural variabilities, homology modeling was further applied as well-established protocol to enrich such valuable data. As a result, 145 mutation-induced spatial variations of 42 DTs, 1622 inter-species structures originating from 292 DTs, 118 outward\/inward-facing conformations belonging to 59 DTs, and 822 xenobiotics-regulated structures in complex with 57 DTs were updated to VARIDT (https:\/\/idrblab.org\/varidt\/ and http:\/\/varidt.idrblab.net\/). All in all, the newly collected structural variabilities will be indispensable for explaining drug sensitivity\/selectivity, bridging preclinical research with clinical trial, revealing the mechanism underlying drug-drug interaction, and so on.<\/jats:p>","DOI":"10.1093\/nar\/gkab1013","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T19:25:40Z","timestamp":1634153140000},"page":"D1417-D1431","source":"Crossref","is-referenced-by-count":88,"title":["VARIDT 2.0: structural variability of drug transporter"],"prefix":"10.1093","volume":"50","author":[{"given":"Tingting","family":"Fu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"},{"name":"Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun\u00a0130023, China"}]},{"given":"Fengcheng","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, Shijiazhuang\u00a0050017, China"}]},{"given":"Jiayi","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"}]},{"given":"Wenqi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Surgery, HKU-SZH & Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}]},{"given":"Xuedong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, Shijiazhuang\u00a0050017, China"}]},{"given":"Xingang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, Shijiazhuang\u00a0050017, China"}]},{"given":"Wenwen","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, Shijiazhuang\u00a0050017, China"}]},{"given":"Chengzhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, Shijiazhuang\u00a0050017, China"}]},{"given":"Lushan","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"}]},{"given":"Jianqing","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China"}]},{"given":"Qingchuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun\u00a0130023, China"}]},{"given":"Su","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-0053","authenticated-orcid":false,"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou\u00a0310058, China"},{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou\u00a0330110, China"}]}],"member":"286","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"2022010507381141000_B1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev-pharmtox-010611-134529","article-title":"Drug transporters in drug efficacy and toxicity","volume":"52","author":"DeGorter","year":"2012","journal-title":"Annu. 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