Coarse grained protein-lipid model with application to lipoprotein particles
Coarse grained protein-lipid model with application to lipoprotein particles
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DOI：
10.1021/jp0550816
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发表时间：
2006-03-02
影响因子：
3.3
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Shih, AY;Arkhipov, A;Schulten, K
将分子动力学模拟的粗粒度模型从脂类扩展到蛋白质。在克莱因开创的这种模型的框架中，原子被描述为珠子，珠子之间的相互作用由有效势控制。这里开发的扩展是基于Marrink等人以前开发的粗粒度脂质模型，虽然未来的版本将调和所采取的方法与克莱因和其他作者的系统方法。蛋白质的每个氨基酸由两个粗粒珠子表示，一个用于主链（所有残基相同），一个用于侧链（取决于残基类型）。粗粒化将系统大小减小了约10倍，并允许25-50 fs的集成时间步长。该模型适用于模拟盘状高密度脂蛋白颗粒，涉及水，脂质，和两个主要的螺旋蛋白。这些粒子是扩展粗粒度模型的理想测试系统。我们的模型被证明是可靠的，在保持预组装颗粒的形状，并在复制高密度脂蛋白的整体结构特征准确。脂蛋白组装的微秒模拟揭示了蛋白质-脂质复合物的形成，其中两种蛋白质连接到盘状脂质双层的两侧。
A coarse-grained model for molecular dynamics simulations is extended from lipids to proteins. In the framework of such models pioneered by Klein, atoms are described group-wise by beads, with the interactions between beads governed by effective potentials. The extension developed here is based on a coarse-grained lipid model developed previously by Marrink et al., although future versions will reconcile the approach taken with the systematic approach of Klein and other authors. Each amino acid of the protein is represented by two coarse-grained beads, one for the backbone (identical for all residues) and one for the side-chain (which differs depending on the residue type). The coarse-graining reduces the system size about 10-fold and allows integration time steps of 25-50 fs. The model is applied to simulations of discoidal high-density lipoprotein particles involving water, lipids, and two primarily helical proteins. These particles are an ideal test system for the extension of coarse-grained models. Our model proved to be reliable in maintaining the shape of preassembled particles and in reproducing the overall structural features of high-density lipoproteins accurately. Microsecond simulations of lipoprotein assembly revealed the formation of a protein-lipid complex in which two proteins are attached to either side of a discoidal lipid bilayer.