Atomistic molecular dynamics simulation analysis of molecular physiological problems involving ion channel activity regulation

涉及离子通道活性调节的分子生理问题的原子分子动力学模拟分析

• 批准号: 21590241
• 负责人: NISHIZAWA Kazuhisa
• 金额: $ 3万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590241/
• 关键词: 生体膜; チャネル; トランスポーター; 脂質ラフト; 計算化学; 脂質膜融合; 分子動力学; 分子シミュレーション; 構造生物化学; 分子生物物理; 自由エネルギー摂動法; 脂質膜; 膜ドメイン構造; コレステロール; 膜融合; 細胞内分子移動; 膜ドメイン形成; SNARE; イオンチャネル; カリウムチャネル

To gain insight into structure-function relationship of Kv channel and other physiological issues, molecular dynamics(MD) simulations were conducted. Atomistic details regarding Kv channel closing mechanism were revealed. We also applied coarse-grained MD simulations to curved membranes, in particular, hemifusion-mimicking membrane systems. The latter analysis showed that lipids with a high degree of negative spontaneous curvature tend to be enriched at the junction of the bilayers that is highly curved. We also showed that cholesterol-dependent formation of lipid microdomains proceeds under strong influence of membrane curvature. The possibility that such curvature dependent localization of microdomains may contribute to the intracellular lipid sorting was discussed.

为了深入了解 Kv 通道的结构功能关系和其他生理问题，进行了分子动力学（MD）模拟。揭示了有关 Kv 通道关闭机制的原子细节。我们还将粗粒度 MD 模拟应用于弯曲膜，特别是半融合模拟膜系统。后一分析表明，具有高度负自发曲率的脂质往往在高度弯曲的双层交界处富集。我们还表明，胆固醇依赖性脂质微区的形成是在膜曲率的强烈影响下进行的。讨论了微区的这种曲率依赖性定位可能有助于细胞内脂质分选的可能性。

项目成果

Molecular dynamics simulation analyses of stalk-inducing effect of viral fusion peptides : importance of oblique orientation in membranes

病毒融合肽茎诱导效应的分子动力学模拟分析：膜倾斜方向的重要性

• 发表时间: 2010
• 期刊: J Biophys Chem
• 作者: Manami Nishizawa;Kazuhisa Nishizawa
• 通讯作者: Kazuhisa Nishizawa

Molecular Dynamics Simulations of Kv Channels and Gating-Modifier Peptide Toxins

Kv 通道和门控修饰肽毒素的分子动力学模拟

• 发表时间: 2009
• 期刊: Current Computer-Aided Drug Design
• 影响因子: 1.7
• 作者: Manami Nishizawa;Kazuhisa Nishizaw;唐木晋一郎;Kazuhisa Nishizawa
• 通讯作者: Kazuhisa Nishizawa

Coupling of S4 helix Translocation and S6 Gating Analyzed by Molecular Dynamic Simulations of Mutated Kv channels

通过突变 Kv 通道的分子动力学模拟分析 S4 螺旋易位和 S6 门控的耦合

• 发表时间: 2009
• 期刊: Biophys J
• 影响因子: 3.4
• 作者: Manami Nishizawa;Kazuhisa Nishizawa
• 通讯作者: Kazuhisa Nishizawa

Atomistic molecular simulation of gating modifier venom peptides-two binding modes and effects of lipid structure. In : Kamkin A(ed). Mechanosensitivity in Cells and Tissues 4 : Mechanosensitivity and Mechanotransduction

门控修饰毒液肽的原子分子模拟——两种结合模式和脂质结构的影响。

• 发表时间: 2010
• 作者: 田副秀章;唐木晋一郎;桑原厚和;Kazuhisa Nishizawa
• 通讯作者: Kazuhisa Nishizawa

Molecular Dymamic Simulations of Kuchaunels

Kuchaunels 的分子动力学模拟

• 发表时间: 2009
• 期刊: Curr. Comput. Aided Drug Des 5
• 作者: 加治いずみ;唐木晋一郎;桑原厚和;Kazuhisa Nishzawa
• 通讯作者: Kazuhisa Nishzawa