Biomechanics Group, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan - Italy.
J Appl Biomater Funct Mater. 2013 Jun 24;11(1):e53-60. doi: 10.5301/JABFM.5000148.
The aim of this work is to analyze the conformational changes in the acetylcholine receptor caused by channel opening and to investigate the electrostatic profile during ion translocation through the channel.
A computational model of the human muscle-type acetylcholine receptor (AChR) was built and used to analyze channel structure and its interactions with different ions. Using the Torpedo AChR crystal structure as a homologous template, the 3D structure of the human muscle-type AChR was reconstructed.
This first model is optimized and an open structure of the channel is generated using Normal Mode Analysis in order to assess morphologic and energetic differences between open and closed structures. In addition, the issue of ion translocation is investigated in further detail. Results elucidate different aspects of the channel: channel gate structure, channel interactions with translocating ions, differences between muscle-type AChR and previous neuronal-type AChR models.
The model constructed here is ideal for further computational studies on muscle-type AChR and its pathologic mutations.
本工作旨在分析乙酰胆碱受体通道开放引起的构象变化，并研究离子通过通道转运过程中的静电分布。
构建了人类肌肉型乙酰胆碱受体（AChR）的计算模型，并用于分析通道结构及其与不同离子的相互作用。使用Torpedo AChR 晶体结构作为同源模板，重建了人类肌肉型 AChR 的 3D 结构。
该模型经过优化，并通过正常模态分析生成了通道的开放结构，以评估开放和关闭结构之间的形态和能量差异。此外，还进一步详细研究了离子转运问题。结果阐明了通道的不同方面：通道门结构、通道与转运离子的相互作用、肌肉型 AChR 与先前的神经元型 AChR 模型之间的差异。
这里构建的模型非常适合进一步研究肌肉型 AChR 及其病理突变的计算。
