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Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods

SEUNGHYUN AHN1, JUNG-YEON LEE1, JIHA SUNG1,2, HYUN JOO KIM3, SEYEON PARK1,2,*

1 Department of Applied Chemistry, Dongduk Women’s University, Seoul, 02748, Korea
2 Division of Applied Chemistry and Cosmetic Science, Dongduk Women’s University, Seoul, 02748, Korea
3 Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, 03722, Korea

* Corresponding Author: SEYEON PARK. Email: email

(This article belongs to the Special Issue: Expert Opinions and Future Trends on Stem Cells, Biomaterials and Growth Factors)

BIOCELL 2023, 47(7), 1661-1673. https://doi.org/10.32604/biocell.2023.027984

Abstract

Background: Although the GABAA receptor (GABAAR) has been proposed as the main action site for sevoflurane, isoflurane, halothane, enflurane, propofol, and benzodiazepines (BZDs), binding of these anesthetics with high-resolution structures of the GABAAR have been rarely examined by comparative docking analyses. Moreover, various combinations of ligands on more GABAARs with various subtypes need to be analyzed to understand the elaborate action mechanism of GABAARs better because some GABAA ligands showed specificity toward the distinct subtypes of the GABAAR. Methods: We performed in silico docking analysis to compare the binding modes of sevoflurane, isoflurane, halothane, enflurane, propofol, and BZDs to the GABAAR based on one of the most recently provided 3D structures. We performed the docking analysis and the affinity-based ranking of the binding sites. Results: Our docking studies revealed that isoflurane, halothane, and enflurane docked in an extracellular domain (ECD) on GABAARs, in contrast to sevoflurane. Conclusion: Our results supported a multi-site mechanism for the allosteric modulation of propofol. Propofol was bound to the pore or favored various subsites in the transmembrane domain (TMD). Our result confirmed that different chemically related BZD ligands interact via distinct binding modes rather than by using a common binding mode, as previously suggested.

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APA Style
AHN, S., LEE, J., SUNG, J., KIM, H.J., PARK, S. (2023). Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods. BIOCELL, 47(7), 1661-1673. https://doi.org/10.32604/biocell.2023.027984
Vancouver Style
AHN S, LEE J, SUNG J, KIM HJ, PARK S. Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods. BIOCELL . 2023;47(7):1661-1673 https://doi.org/10.32604/biocell.2023.027984
IEEE Style
S. AHN, J. LEE, J. SUNG, H.J. KIM, and S. PARK "Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods," BIOCELL , vol. 47, no. 7, pp. 1661-1673. 2023. https://doi.org/10.32604/biocell.2023.027984



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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