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Computational approaches for efficiently predicting such interactions facilitate drug development. Recently, methods based on deep learning, including structure- and sequence-based models, have achieved impressive performance on several different datasets. However, their application still suffers from a generalizability issue because of insufficient data, especially for structure based models, as well as a heterogeneity problem because of different label measurements and varying proteins across datasets. Here, we present an interpretable multi-task model to evaluate protein\u2013ligand interaction (Multi-PLI). The model can run classification (binding or not) and regression (binding affinity) tasks concurrently by unifying different datasets. The model outperforms traditional docking and machine learning on both binary classification and regression tasks and achieves competitive results compared with some structure-based deep learning methods, even with the same training set size. Furthermore, combined with the proposed occlusion algorithm, the model can predict the important amino acids of proteins that are crucial for binding, thus providing a biological interpretation.<\/jats:p>","DOI":"10.1186\/s13321-021-00510-6","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T14:48:47Z","timestamp":1618498127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Multi-PLI: interpretable multi\u2010task deep learning model for unifying protein\u2013ligand interaction datasets"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-1300","authenticated-orcid":false,"given":"Fan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muchun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"510_CR1","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1039\/c2cs35357a","volume":"42","author":"D-L Ma","year":"2013","unstructured":"Ma D-L, Chan DS-H, Leung C-H (2013) Drug repositioning by structure-based virtual screening. 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