{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:36:16Z","timestamp":1791315376973,"version":"4.3.1"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:00:00Z","timestamp":1757203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    G protein\u2010coupled receptor family C, group 5, member D (GPRC5D), a member of the G protein\u2010coupled receptor (GPCR) family, has recently emerged as a promising target for immunotherapy in hematologic malignancies, particularly multiple myeloma. However, no systematic virtual screening studies have been conducted to identify small\u2010molecule inhibitors targeting GPRC5D. To address this gap, a multistep computational screening strategy is developed that integrates Protein\u2212Ligand Affinity prediction NETwork (PLANET), a GPU\u2010accelerated version of AutoDock Vina (Vina\u2010GPU), molecular mechanics\/generalized born surface area (MM\/GBSA), and an online tool for Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) property prediction (admetSAR 3.0), complemented by molecular dynamics (MD) simulations and absolute binding free energy (ABFE). From an initial library of 8,617 compounds, four candidates (compounds 1, 2, 7, and 8) are prioritized. Among them, compound 2 shows relatively strong binding affinity (MM\/GBSA \u0394\n                    <jats:italic>G<\/jats:italic>\n                    = \u221279.8 kcal\u2009mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    , ABFE\u2009=\u2009\u22129.0 kcal\u2009mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and high drug\u2010likeness (quantitative estimate of drug\u2010likeness\u2009=\u20090.670). MD simulations confirm its stable salt bridge interactions with key residues ASP238 and ASP239. This study proposes a systematic virtual screening workflow to facilitate the discovery of GPRC5D\u2010targeted therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/open.202500360","type":"journal-article","created":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T16:39:01Z","timestamp":1757263141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of Potential GPRC5D Inhibitors through Virtual Screening and Molecular Dynamics Simulations"],"prefix":"10.1002","volume":"14","author":[{"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"Bone Marrow Transplantation Center the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 310003 China"},{"name":"Lymphoma Department Zhejiang Cancer Hospital  Hangzhou Zhejiang 310022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinle","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou 310014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roufen","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering Jiangsu University of Technology  Changzhou 213001 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-4372","authenticated-orcid":false,"given":"Xiaowu","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-3804","authenticated-orcid":false,"given":"Zhen","family":"Cai","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 310003 China"},{"name":"Institute of Hematology Zhejiang University  Hangzhou Zhejiang 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.2128"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27422"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.0003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2015.03.008"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00527-y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25791"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2024.2370552"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1394048"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01611-z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00966-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6226"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2152-2650(21)02229-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003342"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003805"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau7746"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-1216"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209900"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(22)00372-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49625-y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1010"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","unstructured":"P.Yan X.Lin F.Xu Orphan receptor GPRC5D in complex with scFv150\u2010182024.https:\/\/doi.org\/10.2210\/pdb8yzk\/pdb.","DOI":"10.2210\/pdb8yzk\/pdb"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2024.168748"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","unstructured":"J.Jeong J.Shin J.Park Y.Cho Cryo\u2010EM structure for the GPRC5D complexed with Talquetamab Fab(2024). https:\/\/doi.org\/10.2210\/pdb9IMA\/pdb.","DOI":"10.2210\/pdb9ima\/pdb"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.167994"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-007-9133-z"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00302"},{"key":"e_1_2_9_29_1","unstructured":"Schr\u00f6dinger Release 2021\u20102: LigPrep Schr\u00f6dinger LLC New York NY 2021."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.4c00664"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-83730-8"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.3c00253"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27093041"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2021.1942836"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030644s"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.23106"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae298"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1808117"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02491-5"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01461-1"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-023-03559-4"}],"container-title":["ChemistryOpen"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/open.202500360","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T05:21:40Z","timestamp":1764998500000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/open.202500360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,7]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/open.202500360"],"URL":"https:\/\/doi.org\/10.1002\/open.202500360","archive":["Portico"],"relation":{},"ISSN":["2191-1363","2191-1363"],"issn-type":[{"value":"2191-1363","type":"print"},{"value":"2191-1363","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,7]]},"assertion":[{"value":"2025-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500360"}}