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In this work, we have investigated the interactions of benzothiadiazine with the basic components of cell membranes and solvents, such as phospholipids, cholesterol, ions, and water. The analysis of the mutual microscopic interactions is of central importance to elucidate the local structure of benzothiadiazine as well as the mechanisms responsible for the access of benzothiadiazine to the interior of the cell. We have performed molecular dynamics simulations of benzothiadiazine embedded in three different model zwitterionic bilayer membranes made by dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, 1,2-dioleoyl-sn-glycero-3-phosphoserine, and cholesterol inside aqueous sodium-chloride solution in order to systematically examine microscopic interactions of benzothiadiazine with the cell membrane at liquid-crystalline phase conditions. From data obtained through radial distribution functions, hydrogen-bonding lengths, and potentials of mean force based on reversible work calculations, we have observed that benzothiadiazine has a strong affinity to stay at the cell membrane interface although it can be fully solvated by water in short periods of time. Furthermore, benzothiadiazine is able to bind lipids and cholesterol chains by means of single and double hydrogen-bonds of different characteristic lengths.<\/jats:p>","DOI":"10.1063\/5.0065163","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T17:35:27Z","timestamp":1633023327000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Structure of benzothiadiazine at zwitterionic phospholipid cell membranes"],"prefix":"10.1063","volume":"155","author":[{"given":"Zheyao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Physics, Technical University of Catalonia-Barcelona Tech, B5-209 Northern Campus UPC 1 , 08034 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3721-9634","authenticated-orcid":false,"given":"Jordi","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Department of Physics, Technical University of Catalonia-Barcelona Tech, B5-209 Northern Campus UPC 1 , 08034 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2731-5283","authenticated-orcid":false,"given":"Huixia","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai Jiao Tong University 2 , 800 Dongchuan Road, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"317","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"2023062603464487700_c1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/s0304-4157(00)00016-2","volume":"1469","year":"2000","journal-title":"Biochim. 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