Next Article in Journal
Actinomycin V Inhibits Migration and Invasion via Suppressing Snail/Slug-Mediated Epithelial-Mesenchymal Transition Progression in Human Breast Cancer MDA-MB-231 Cells In Vitro
Previous Article in Journal
Experimental and Computational Study to Reveal the Potential of Non-Polar Constituents from Hizikia fusiformis as Dual Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitors
Open AccessArticle

Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations

1
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
2
Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China
3
Innovation Center for Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(5), 303; https://doi.org/10.3390/md17050303
Received: 23 April 2019 / Revised: 10 May 2019 / Accepted: 17 May 2019 / Published: 23 May 2019
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are involved in fast synaptic transmission and mediated physiological activities in the nervous system. α-Conotoxin ImI exhibits subtype-specific blockade towards homomeric α7 and α9 receptors. In this study, we established a method to build a 2×ImI-dendrimer/h (human) α7 nAChR model, and based on this model, we systematically investigated the molecular interactions between the 2×ImI-dendrimer and hα7 nAChR. Our results suggest that the 2×ImI-dendrimer possessed much stronger potency towards hα7 nAChR than the α-ImI monomer and demonstrated that the linker between α-ImI contributed to the potency of the 2×ImI-dendrimer by forming a stable hydrogen-bond network with hα7 nAChR. Overall, this study provides novel insights into the binding mechanism of α-ImI dendrimer to hα7 nAChR, and the methodology reported here opens an avenue for the design of more selective dendrimers with potential usage as drug/gene carriers, macromolecular drugs, and molecular probes. View Full-Text
Keywords: 2×ImI-dendrimer; hα7 nAChR; linker; binding affinity; molecular dynamics simulation; MMGB/SA 2×ImI-dendrimer; hα7 nAChR; linker; binding affinity; molecular dynamics simulation; MMGB/SA
Show Figures

Figure 1

MDPI and ACS Style

Xu, X.; Liang, J.; Zhang, Z.; Jiang, T.; Yu, R. Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations. Mar. Drugs 2019, 17, 303.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop