γ-Aminobutyric acid type-A receptors (GABARs) play a critical role in neural transmission by mediating the inhibitory neural firing and are the target of many psychiatric drugs. Among them, propofol is one of the most widely used and important general anesthetics in clinics. Recent advances in structural biology revealed the structure of a human GABAR in both open and closed states. Yet, the detailed mechanism of the receptor and propofol remains to be fully understood. Therefore, in this study, based on the previous successes in structural biology, a variety of computational techniques were applied to fill the gap between previous experimental studies. This study investigated the ion-conducting mechanism of GABAR, predicted the possible binding mechanism of propofol, and revealed a new motion mechanism of transmembrane domain (TMD) helices. We hope that this study may contribute to future studies on ion-channel receptors, general anesthetics, and drug development.
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