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The different polymorphs show conformational changes in the macrocyclic core, as well as the cyclopropylsulfonamide and methylpyrazinamide substituents. Molecular docking shows that one of the conformations fits well into the active site pocket of the NS3\/4A serine protease target, and can interact with the pocket and catalytic triad via hydrophobic interactions and hydrogen bonds. These results can provide further insight for optimization of the binding of acylsulfonamide inhibitors to the NS3\/4A serine protease. In addition, this also demonstrate the opportunity of deriving different polymorphs and distinct macrocycle conformations from the same experiments using MicroED.<\/jats:p>","DOI":"10.1101\/2023.09.09.556999","type":"posted-content","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:25:11Z","timestamp":1694391911000},"source":"Crossref","is-referenced-by-count":2,"title":["Polymorphic Structure Determination of the Macrocyclic Drug Paritaprevir by MicroED"],"prefix":"10.64898","author":[{"given":"G","family":"Bu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Danelius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.H","family":"Wieske","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-4069","authenticated-orcid":false,"given":"T","family":"Gonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"8","key":"2023091410050610000_2023.09.09.556999v1.1","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1021\/cm00044a013","article-title":"Solid-State Pharmaceutical Chemistry","volume":"6","year":"1994","journal-title":"Chem. 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