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 nonequivalent 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.

α7烟碱乙酰胆碱受体是Cys环超家族的同源五聚体离子通道，其特点是开放概率低、钙渗透性高和快速脱敏。 α7 受体已被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。尽管其功能很重要，但 α7 受体的计算机研究无法产生解释受体激活的结构特征的通用模型，也无法预测各种配体类别的作用模式。 α7 nAChR 建模中的两个特殊问题是缺乏高分辨率结构和存在五个潜在不等价的正构配体结合位点。用于同源建模的模板、研究的配体类型、模拟方法和模拟时间存在很大的差异。然而，尚未进行针对α7建模方法学异同的系统调查。在这项工作中，我们通过比较计算研究的结果以及结构研究、配体结合研究以及与其他 nAChR 比较等主要主题下的实验研究，对 α7 nAChR 的建模文献进行了批判性分析。根据我们的发现，我们还总结了该领域当前的问题，并为未来有关 α7 受体建模的研究提出了建议。