{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T21:12:00Z","timestamp":1776114720491,"version":"3.50.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nowadays, the complexity of disease mechanisms and the inadequacy of single-target therapies in restoring the biological system have inevitably instigated the strategy of multi-target therapeutics with the analysis of each target individually. However, it is not suitable for dealing with the conflicts between targets or between drugs. With the release of high-precision protein structure prediction artificial intelligence, large-scale high-precision protein structure prediction and docking have become possible. In this article, we propose a multi-target drug discovery method by the example of therapeutic hypothermia (TH). First, we performed protein structure prediction for all protein targets of each group by AlphaFold2 and RoseTTAFold. Then, QuickVina 2 is used for molecular docking between the proteins and drugs. After docking, we use PageRank to rank single drugs and drug combinations of each group. The ePharmaLib was used for predicting the side effect targets. Given the differences in the weights of different targets, the method can effectively avoid inhibiting beneficial proteins while inhibiting harmful proteins. So it could minimize the conflicts between different doses and be friendly to chronotherapeutics. Besides, this method also has potential in precision medicine for its high compatibility with bioinformatics and promotes the development of pharmacogenomics and bioinfo-pharmacology.<\/jats:p>","DOI":"10.1093\/bib\/bbac365","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T11:54:40Z","timestamp":1661342080000},"source":"Crossref","is-referenced-by-count":6,"title":["A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia"],"prefix":"10.1093","volume":"23","author":[{"given":"Fei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Institute of Emergency Medicine, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"}]},{"given":"Xiangkang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Institute of Emergency Medicine, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"}]},{"given":"Jingyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Institute of Emergency Medicine, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"}]},{"given":"Jiawei","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Institute of Emergency Medicine, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7919-8213","authenticated-orcid":false,"given":"Mao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Institute of Emergency Medicine, Zhejiang University , Hangzhou 310009, Zhejiang Province, China"},{"name":"Key Laboratory of The Diagnosis and Treatment of Severe Trauma and 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