Structural and Informatics Basis of Channel Protein Interactions

通道蛋白相互作用的结构和信息学基础

• 批准号: 12144206
• 负责人: NAKAMURA Haruki
• 金额: $ 17.66万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12144206/
• 关键词: Molecular Dynamics; Homology Modeling; Molecular Recognition; Simulation; Supramolecular Structure; Molecular Surface; Brownian Dynamics; Database; チャネル蛋白質; ループ構造; 構造探索; マルチカノニカル統計

Methods were developed for building tertiary structural models of channel proteins, by combining the inductive homology modeling method and the deductive molecular simulation for low-homologous regions. In particular, we developed a new model building method for flexible loop regions, based on the Force-Biased Multicanonical Molecular Dynamics (FB-McMD) with the implicit solvent model using the generalized Born approximation. This method could give us a precise protein model structure even for the flexible loop regions, and it was applied to modeling of actual channel proteins. In addition, protein functions with their sites and protein-protein interaction pairs were identified and predicted with the informatics technology using our new databases, eF-site and HINTdb, respectively.In order to analyze the molecular recognition of channel proteins, we have developed a new NMR analysis method, where the complexed structure is produced by molecular dynamics simulations using the cross saturation transfer and the residual dipolar coupling signals. This method was applied to build a complexed model between KcsA K^+-channel and agitoxin-2. Brownian dynamics simulation method was also developed for computing permeation of small ions and compounds through a channel protein.

结合归纳同源建模方法和低同源区域演绎分子模拟方法，建立了通道蛋白三级结构模型的方法。特别是，我们基于力偏向多正则分子动力学 (FB-McMD) 和使用广义玻恩近似的隐式溶剂模型，开发了一种用于柔性环区域的新模型构建方法。即使对于柔性环区域，该方法也可以为我们提供精确的蛋白质模型结构，并将其应用于实际通道蛋白的建模。此外，分别使用我们的新数据库 eF-site 和 HINTdb，通过信息学技术识别和预测了蛋白质功能及其位点和蛋白质-蛋白质相互作用对。为了分析通道蛋白的分子识别，我们开发了一种新的 NMR 分析方法，其中使用交叉饱和转移和残留偶极耦合信号通过分子动力学模拟产生复杂结构。该方法用于建立 KcsA K^+-通道和 agitoxin-2 之间的复杂模型。还开发了布朗动力学模拟方法，用于计算小离子和化合物通过通道蛋白的渗透。

项目成果

Ono, Satoshi: "Calibration of force-field dependency in free energy landscapes of peptide caonformations by quantum chemical calculations"Journal of Computational Chemistry. vol.23,No.4. 470-476 (2002)

小野聪：“通过量子化学计算校准肽构象自由能景观中的力场依赖性”计算化学杂志。

Kinoshita, Kengo: "Identification of protein functions from a molecular surface database, eF-site"Journal of Structural and Functional Genomics. vol.2,No.1. 9-22 (2001)

Kinoshita，Kengo：“从分子表面数据库识别蛋白质功能，eF-site”结构与功能基因组学杂志。

Bioscience series 9.

生物科学系列9.

• 发表时间: 2004
• 作者: Kinoshita K;et al.
• 通讯作者: et al.

Biology to learn medicine : VI.

生物学学医学：六．

• 发表时间: 2003
• 作者: Nakamura H.

Molecular design of proteins.

蛋白质的分子设计。

• 发表时间: 2001
• 作者: Furukawa K;et al.
• 通讯作者: et al.