Theoretical study of the binding profile of an allosteric modulator NS-1738 with a chimera structure of the α7 nicotinic acetylcholine receptor
Literature Information
Guanglin Kuang, Xu Wang, Christer Halldin, Agneta Nordberg, Bengt Långström, Hans Ågren, Yaoquan Tu
Potentiation of the function of the α7 nicotinic acetylcholine receptor (α7-nAChR) is believed to provide a possible way for the treatment of cholinergic system dysfunctions such as Alzheimer's disease and schizophrenia. Positive allosteric modulators (PAMs) are able to augment the peak current response of the endogenous agonist of α7-nAChR by binding to some allosteric sites. In this study, the binding profile of a potent type I PAM, NS-1738, with a chimera structure (termed α7-AChBP) constructed from the extracellular domain of α7-nAChR and an acetylcholine binding protein was investigated with molecular docking, molecular dynamics simulation, and free energy calculation methods. We found that NS-1738 could bind to three allosteric sites of α7-AChBP, namely, the top pocket, the vestibule pocket and the agonist sub-pocket. NS-1738 has moderate binding affinities (−6.76 to −9.15 kcal mol−1) at each allosteric site. The urea group is critical for binding and can form hydrogen-bond interactions with the protein. The bulky trifluoromethyl group also has a great impact on the binding modes and binding affinities. We believe that our study provides valuable insight into the binding profiles of type I PAMs with α7-nAChR and is helpful for the development of novel PAMs.
Recommended Journals

Acta Materialia

Current Opinion in Solid State & Materials Science

Journal of Natural Medicines

Russian Chemical Bulletin

Russian Journal of Applied Chemistry

Chemical Communications

Russian Journal of Coordination Chemistry

New Journal of Chemistry

Journal of Saudi Chemical Society

Saudi Pharmaceutical Journal
Related Literature
Morphology engineering of high performance binary oxide electrodes
Kunfeng Chen, Congting Sun, Dongfeng Xue
DOI: 10.1039/C4CP03888F
Protonation induced shifting of electron-accepting centers in intramolecular charge transfer chromophores: a theoretical study
Tao Tang, Hong Chi, Tingting Lin
DOI: 10.1039/C4CP02410A
The Crystal-T algorithm: a new approach to calculate the SLE of lipidic mixtures presenting solid solutions
Guilherme J. Maximo, Mariana C. Costa, Antonio J. A. Meirelles
DOI: 10.1039/C4CP01529K
Silicon-pyrene/perylene hybrids as molecular rectifiers
Kavita Garg, Chiranjib Majumder, Sandip K. Nayak, Dinesh K. Aswal, Shiv K. Gupta, Subrata Chattopadhyay
DOI: 10.1039/C4CP04044A
An efficient method to enhance the stability of sulphide semiconductor photocatalysts: a case study of N-doped ZnS
Yansong Zhou, Gang Chen, Yaoguang Yu, Yujie Feng, Yi Zheng, Fang He, Zhonghui Han
DOI: 10.1039/C4CP03736G
Photoelectrocatalytic degradation of rhodamine B on TiO2 photonic crystals
Xiuzhen Zheng, Danzhen Li, Xiaofang Li, Linhui Yu, Peng Wang, Xiaoyun Zhang, Jialin Fang, Yu Shao, Yi Zheng
DOI: 10.1039/C4CP01888E
The catalytic formation of leukotriene C4: a critical step in inflammatory processes
Corey A. MacDonald, James W. Gauld, Russell J. Boyd
DOI: 10.1039/C4CP01984A
The substituent effect on the MLCT excited state dynamics of Cu(i) complexes studied by femtosecond time-resolved absorption and observation of coherent nuclear wavepacket motion
Linqiang Hua, Munetaka Iwamura
DOI: 10.1039/C4CP03843F
Modelling analysis of the structure and porosity of covalent triazine-based frameworks
Christian Reece, David J. Willock, Abbie Trewin
DOI: 10.1039/C4CP04046E
Towards bulk thermodynamics via non-equilibrium methods: gaseous methane as a case study
Mirco Zerbetto, Diego Frezzato
DOI: 10.1039/C4CP03815K
You might also like
Is 2-(2-chloroacetamido)-3-phenylpropanoic acid (CAS: 7765-11-9) safe?
2-(2-Chloroacetamido)-3-phenylpropanoic acid (CAS: 7765-11-9) is generally consi...
Is 2-(Benzyloxy)-5-bromobenzoic acid (CAS: 62176-31-2) safe?
2-(Benzyloxy)-5-bromobenzoic acid can be handled safely if appropriate precautio...
What is (4-Methyl-1,2,5-oxadiazol-3-yl)methanamine hydrochloride (CAS: 1159825-48-5)?
(4-Methyl-1,2,5-oxadiazol-3-yl)methanamine hydrochloride is a chemical compound ...
What is 2-(5-Hexylthiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAS: 917985-54-7)?
2-(5-Hexylthiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAS: 917985-54...
Are there alternatives to 4-(8-Methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)benzenamine (CAS: 102771-26-6) in synthesis?
While 4-(8-Methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)benzenamine (CAS:...
What is the market or research trend for tert-butyl 3-hydroxy-4,5,7,8-tetrahydro-2H-pyrazolo[3,4-d]azepine-6-carboxylate (CAS: 851376-80-2)?
The market for tert-butyl 3-hydroxy-4,5,7,8-tetrahydro-2H-pyrazolo[3,4-d]azepine...
How should waste containing 3,5-Diamino-1H-pyrazole-4-carbonitrile (CAS: 6844-58-2) be handled?
Waste containing 3,5-Diamino-1H-pyrazole-4-carbonitrile (CAS: 6844-58-2) should ...
How is (6-Fluoro-3-pyridinyl)boronic acid (CAS: 351019-18-6) typically synthesized?
(6-Fluoro-3-pyridinyl)boronic acid can be synthesized through the reaction of 6-...
What industries use Dibenzyl carbonimidoylbiscarbamate (CAS: 10065-79-9)?
Dibenzyl carbonimidoylbiscarbamate (CAS: 10065-79-9) finds applications in vario...
What is the market or research trend for (beta,beta,2,3,4,5,6-~2~H_7_)Phenylalanine (CAS: 74228-83-4)?
The market for (beta,beta,2,3,4,5,6-~2~H_7_)Phenylalanine (CAS: 74228-83-4) is g...
Source Journal
Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.
![(1R)-N-((1R)-1-Phenylethyl)-1-[4-(tert-butyldimethylsilyloxymethyl)cyclohexyl]ethan-1-amine structure (1R)-N-((1R)-1-Phenylethyl)-1-[4-(tert-butyldimethylsilyloxymethyl)cyclohexyl]ethan-1-amine structure](https://static.chemtradehub.com/structs/672/672314-45-3-47ef.webp)
![3,7-Di(1,1':3',1''-terphenyl-5'-yl)-10,11,12,13-tetrahydrodiindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphocin-5-ol 5-oxide structure 3,7-Di(1,1':3',1''-terphenyl-5'-yl)-10,11,12,13-tetrahydrodiindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphocin-5-ol 5-oxide structure](https://static.chemtradehub.com/structs/135/1352810-38-8-3f10.webp)


