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Rubraxanthone exhibited mixed-inhibition antiviral activity against SARS-CoV-2 M\n                    <jats:sup>pro<\/jats:sup>\n                    , relatively low cytotoxicity, and high cellular inhibition. However, the atomic inhibition mechanism remains ambiguous. LB-PaCS-MD\/FMO is a hybrid ligand-binding evaluation method elucidating how rubraxanthone interacts with SARS-CoV-2 M\n                    <jats:sup>pro<\/jats:sup>\n                    . In the first step, LB-PaCS-MD, which is regarded as a flexible docking, efficiently samples a set of ligand-binding pathways. After that, a reasonable docking pose of LB-PaCS-MD is evaluated by the FMO calculation to elucidate a set of protein\u2013ligand interactions, enabling one to know the binding affinity of a specified ligand with respect to a target protein. A possible conformation was proposed for rubraxanthone binding to the SARS-CoV-2 M\n                    <jats:sup>pro<\/jats:sup>\n                    active site, and allosteric inhibition was elucidated by combining blind docking with\n                    <jats:italic>k<\/jats:italic>\n                    -means clustering. The interaction profile, key binding residues, and considerable interaction were elucidated for rubraxanthone binding to both M\n                    <jats:sup>pro<\/jats:sup>\n                    sites. Integrated LB-PaCS-MD\/FMO provided a more reasonable complex structure for ligand binding at the SARS-CoV-2 M\n                    <jats:sup>pro<\/jats:sup>\n                    active site, which is vital for discovering and designing antiviral drugs.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-22703-1","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T10:03:32Z","timestamp":1666778612000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD\/FMO"],"prefix":"10.1038","volume":"12","author":[{"given":"Kowit","family":"Hengphasatporn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuhei","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patcharin","family":"Wilasluck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peerapon","family":"Deetanya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin R.","family":"Sukandar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warinthorn","family":"Chavasiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aphinya","family":"Suroengrit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwaporn","family":"Boonyasuppayakorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittikhun","family":"Wangkanont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"22703_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-0332-0","author":"A Du Toit","year":"2020","unstructured":"Du Toit, A. 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