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- W4206628652 endingPage "351" @default.
- W4206628652 startingPage "340" @default.
- W4206628652 abstract "Human serotine transporter (hSERT) is one of the most influential drug targets, and its allosteric modulators (e.g., escitalopram) have emerged to be the next-generation medication for psychiatric disorders. However, the molecular mechanism underlying the allosteric modulation of hSERT is still elusive. Here, the simulation strategies of conventional (cMD) and steered (SMD) molecular dynamics were applied to investigate this molecular mechanism from distinct perspectives. First, cMD simulations revealed that escitalopram's binding to hSERT's allosteric site simultaneously enhanced its binding to the orthosteric site. Then, SMD simulation identified that the occupation of hSERT's allosteric site by escitalopram could also block its dissociation from the orthosteric site. Finally, by comparing the simulated structures of two hSERT-escitalopram complexes with and without allosteric modulation, a new conformational coupling between an extracellular (Arg104-Glu494) and an intracellular (Lys490-Glu494) salt bridge was identified. In summary, this study explored the mechanism underlying the allosteric modulation of hSERT by collectively applying two MD simulation strategies, which could facilitate our understanding of the allosteric modulations of not only hSERT but also other clinically important therapeutic targets." @default.
- W4206628652 created "2022-01-26" @default.
- W4206628652 creator A5026655079 @default.
- W4206628652 creator A5027345342 @default.
- W4206628652 creator A5066943426 @default.
- W4206628652 creator A5068598869 @default.
- W4206628652 creator A5072011626 @default.
- W4206628652 creator A5076458955 @default.
- W4206628652 date "2022-01-18" @default.
- W4206628652 modified "2023-10-18" @default.
- W4206628652 title "Molecular Mechanism for the Allosteric Inhibition of the Human Serotonin Transporter by Antidepressant Escitalopram" @default.
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