In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.
In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.
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DOI：
10.2174/1389557520666200130105256
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Horenstein N
中科院分区：
文献类型：
--
作者：
Gulsevin A;Papke RL;Horenstein N
α7烟碱乙酰胆碱受体是Cys环超家族的同型五聚体离子通道，其特征在于其低开放概率、高钙渗透性和快速脱敏。α7受体已被靶向用于治疗精神分裂症、抑郁症和阿尔茨海默病的认知症状，但它也作为胆碱能抗炎途径的一部分参与炎症调节。尽管α7受体在功能上很重要，但其计算机模拟研究不能产生解释受体活化结构特征的通用模型，也不能预测各种配体类别的作用模式。在模拟α7 nAChR中存在两个特殊的问题，即缺乏高分辨率结构和存在5个潜在的非等效正构配体结合位点。关于用于同源性建模的模板、研究的配体类型、模拟方法和模拟时间存在广泛的可变性。然而，尚未对α7建模方法的异同进行系统的调查。在这项工作中，我们通过比较计算研究的结果与其他研究的主要主题下的结构研究，配体结合的研究，并与其他nAChR的比较实验研究，α7 nAChR的建模文献进行了批判性分析。根据我们的研究结果，我们还总结了该领域目前存在的问题，并对未来的研究提出了建议，有关建模的α7受体。
The α7 nicotinic acetylcholine receptor is a homopentameric ion-channel of the Cys-loop superfamily characterized by its low probability of opening, high calcium permeability, and rapid desensitization. The α7 receptor has been targeted for the treatment of the cognitive symptoms of schizophrenia, depression, and Alzheimer’s disease, but it is also involved in inflammatory modulation as a part of the cholinergic anti-inflammatory pathway. Despite its functional importance, in silico studies of the α7 receptor cannot produce a general model explaining the structural features of receptor activation, nor predict the mode of action for various ligand classes. Two particular problems in modeling the α7 nAChR are the absence of a high-resolution structure and the presence of five potentially non-equivalent orthosteric ligand binding sites. There is wide variability regarding the templates used for homology modeling, types of ligands investigated, simulation methods, and simulation times. However, a systematic survey focusing on the methodological similarities and differences in modeling α7 has not been done. In this work, we make a critical analysis of the modeling literature of α7 nAChR by comparing the findings of computational studies with each other and with experimental studies under the main topics of structural studies, ligand binding studies, and comparisons with other nAChR. In light of our findings, we also summarize current problems in the field and make suggestions for future studies concerning modeling of the α7 receptor.
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影响因子：
2.2
作者：
Bisson, William H.;Westera, Gerrit;Scapozza, Leonardo
通讯作者：
Scapozza, Leonardo
DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Bahar, I;Atilgan, AR;Erman, B
通讯作者：
Erman, B
影响因子：
3.5
作者：
Akdemir, Atilla;Edink, Ewald;de Esch, Iwan J. P.
通讯作者：
de Esch, Iwan J. P.
影响因子：
4.2
作者：
Armishaw CJ
通讯作者：
Armishaw CJ
影响因子：
4.8
作者：
Celie, PHN;Klaassen, RV;Sixma, TK
通讯作者：
Sixma, TK