Molecular simulation - based analysis of signal transduction system in neuronal cells

基于分子模拟的神经细胞信号转导系统分析

基本信息

批准号：
16500245
负责人：
NISHIZAWA Kazuhisa
金额：
$ 2.37万
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：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500245/
关键词：
Molecular dynamics computational chemistry シミュレーション Kチャンネル

项目摘要

Our initial goal was molecular dynamics simulation-based study of dynamics of the molecules interacting with PIP2 in presynaptic termini. While we confirmed that molecular orbital calculation and molecular simulations with Gromacs and NAMD packages work on our system, strong interaction due to phosphate groups of PIP2 made the time required for equilibration too long for simulaiton study. Hanatoxin (HaTx) is an ellipsoidal-shaped peptide that binds to the voltage sensor of voltage dependent channels. Of physicochemical interest, HaTx has a ‘ring' of charged residues around its periphery and a hydrophobic protrusion. It has previously been postulated that HaTx binds to and functions on the surface of membranes, but a recent fluorescent-quenching study has implied a fairly deep positioning of HaTx in the lipid bilayer membrane. We carried out numerous molecular dynamic simulations of HaTx1, a well-studied variant of HaTx, in fully hydrated phospholipid bilayers, using two different force … More fields, Gromacs and Charmm. The system reproduced the surface binding mode of HaTx1, in which HaTx1 resided in the extracellular-side (outer) water/membrane interface with the hydrophobic patch of HaTx1 facing the membrane interior. On the other hand, analyses with various parameter settings suggested that the surface binding mode was unstable because of the substantial attractive electrostatic force between HaTx1 and the lipid head groups of the inner (opposite) leaflet. Compared with this electrostatic force, the energetic cost for membrane deformation involving meniscus formation appeared to be small. In an attempt to interpret the quenching data, we consider the possibility of dimpling (meniscus formation) that brings HaTx1 inward (only 〜0.7-0.8 nm above the bilayer center), while accounting for the flexibility of both leaflets of the membrane and the long-range interaction between positively charged residues of the membrane-bound peptide and the polar head groups of the opposite leaflet of the membrane. It is suggested that molecular dynamics simulations taking into account the flexibility of the membrane surface is potentially useful in interpreting the fluorescence-quenching data. Less

我们最初的目标是基于分子动力学模拟研究突触前末端与 PIP2 相互作用的分子动力学。虽然我们确认了 Gromacs 和 NAMD 软件包的分子轨道计算和分子模拟在我们的系统上有效，但 PIP2 的磷酸基团具有强相互作用。使得平衡所需的时间对于模拟研究而言太长。出于物理化学的兴趣，HaTx 的外围有一个带电残基的“环”和一个疏水性突起，此前曾假设 HaTx 与膜表面结合并发挥作用，但最近的一项荧光猝灭研究表明其定位相当深。我们对 HaTx1（经过充分研究的 HaTx 变体）在完全水合磷脂中进行了多次分子动力学模拟。双层，使用两种不同的力场，Gromacs 和 Charmm，该系统再现了 HaTx1 的表面结合模式，其中 HaTx1 位于细胞外侧（外部）水/膜界面，HaTx1 的疏水斑块面向膜内部。另一方面，各种参数设置的分析表明，由于 HaTx1 和内部（相对）的脂质头基之间存在显着的静电力，表面结合模式不稳定。与这种静电力相比，涉及弯月面形成的膜变形的能量消耗似乎很小。在试图解释淬火数据时，我们考虑了使 HaTx1 向内的凹坑（弯月面形成）的可能性（仅~0.7-）。双层中心上方 0.8 nm），同时考虑到膜两个小叶的灵活性以及膜结合肽的带正电残基与极性头基之间的长程相互作用建议考虑膜表面的灵活性的分子动力学模拟对于解释荧光猝灭数据可能有用。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Interaction between k^+ channel gate modifier hanatoxin and lipid bilayer membranes analyzed by mclecular dynamics simmkitin.

通过分子动力学 simmkitin 分析 k^ 通道门调节剂韩毒素和脂质双层膜之间的相互作用。

DOI：
发表时间：
2006
期刊：
Eur. Biophys. J in press
影响因子：
0
作者：
Hishikawa N;Hashizume Y;Yoshida M;Niwa J;Tanaka F;Sobue G.;大西浩史ら;Manami Nishizawa
通讯作者：
Manami Nishizawa

Interaction between K(+) channel gate modifier hanatoxin and lipid bilayer-membranes analysed by molecular dynamics simulation

通过分子动力学模拟分析 K( ) 通道门控修饰剂花毒素与脂质双层膜之间的相互作用