biostudies-literatureUnknown13Yang KGastrin plays important role in stimulating the initiation and development of many gastrointestinal diseases through interacting with the cholecystokinin 2 receptor (CCK2R). The smallest bioactive unit of gastrin activating CCK2R is the C-terminal tetrapeptide capped with an indispensable amide end. Understanding the mechanism of this smallest bioactive unit interacting with CCK2R on a molecular basis could provide significant insights for designing CCK2R antagonists, which can be used to treat gastrin-related diseases. To this end, we performed extensive Gaussian accelerated molecular dynamics simulations to investigate the interaction between gastrin C-terminal pentapeptide capped with/without amide end and CCK2R. The amide cap influences the binding modes of the pentapeptide with CCK2R Frontiers in pharmacology1054575https://www.ebi.ac.uk/biostudies/studies/S-EPMC9899899biostudies-literatureElucidating the molecular determinants in the process of gastrin C-terminal pentapeptide amide end activating cholecystokinin 2 receptor by Gaussian accelerated molecular dynamics simulations.PMC9899899Jin HYang KWang GCGao XZhang GQfalseElucidating the molecular determinants in the process of gastrin C-terminal pentapeptide amide end activating cholecystokinin 2 receptor by Gaussian accelerated molecular dynamics simulations.Gastrin plays important role in stimulating the initiation and development of many gastrointestinal diseases through interacting with the cholecystokinin 2 receptor (CCK2R). The smallest bioactive unit of gastrin activating CCK2R is the C-terminal tetrapeptide capped with an indispensable amide end. Understanding the mechanism of this smallest bioactive unit interacting with CCK2R on a molecular basis could provide significant insights for designing CCK2R antagonists, which can be used to treat gastrin-related diseases. To this end, we performed extensive Gaussian accelerated molecular dynamics simulations to investigate the interaction between gastrin C-terminal pentapeptide capped with/without amide end and CCK2R. The amide cap influences the binding modes of the pentapeptide with CCK2R 2022-01-01T00:00:00Z20222026-05-29T03:35:37.506Z2024-11-19T23:22:09.524ZS-EPMC98998993675614510.3389/fphar.2022.1054575