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CHARMM Force-Field Parameters for Morphine, Heroin, and Oliceridine, and Conformational Dynamics of Opioid Drugsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 29 сентября 2021 г.
- Авторы: Giannos Thomas, Lešnik Samo, Bren Urban, Hodošček Milan, Domratcheva Tatiana, Bondar Ana-Nicoleta
- Журнал: Journal of Chemical Information and Modeling
- Том: 31
- Номер: 8
- Год издания: 2021
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 3964
- Последняя страница: 3977
- Номер статьи: acs.jcim.1c00667
- DOI: 10.1021/acs.jcim.1c00667
- Аннотация: Opioid drug binding to specialized G protein-coupled receptors (GPCRs) can lead to analgesia upon activation via downstream Gi protein signaling and to severe side effects via activation of the β-arrestin signaling pathway. Knowledge of how different opioid drugs interact with receptors is essential, as it can inform and guide the design of safer therapeutics. We performed quantum and classical mechanical computations to explore the potential energy landscape of four opioid drugs: morphine and its derivatives heroin and fentanyl and for the unrelated oliceridine. From potential energy profiles for bond twists and from interactions between opioids and water, we derived a set of force-field parameters that allow a good description of structural properties and intermolecular interactions of the opioids. Potential of mean force profiles computed from molecular dynamics simulations indicate that fentanyl and oliceridine have complex energy landscapes with relatively small energy penalties, suggesting that interactions with the receptor could select different binding poses of the drugs.
- Добавил в систему: Домрачева Татьяна Михайловна