Collective Dynamics of Large Proteins from Mixed Coarse‐Grained Elastic Network Model
Collective Dynamics of Large Proteins from Mixed Coarse‐Grained Elastic Network Model
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DOI：
10.1002/qsar.200430922
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发表时间：
2005-06
期刊：
影响因子：
--
通讯作者：
O. Kurkcuoglu;R. Jernigan;P. Doruker
中科院分区：
文献类型：
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作者：
O. Kurkcuoglu;R. Jernigan;P. Doruker
弹性网络模型是一种粗粒度的正态模式分析，被广泛用于研究蛋白质及其复合物的重要功能集体运动。近年来，在弹性网络模型中引入了混合粗粒化方法，从而可以用低分辨率和高分辨率的区域来模拟蛋白质的天然构象。在混合分辨率模型中，弹性网络的每个节点既可以代表单个原子（高分辨率），也可以代表残馀原子（低分辨率），相邻节点通过谐波弹簧连接。在这里，高分辨率的部分构成了蛋白质的有趣部分，如活性位点，而结构的其余部分以较低的分辨率保留。通过对所得到的网络进行正常模式分析，可以以合理的计算效率分析超分子组合的集体动力学（低频模式）和随之而来的构象变化，这可能作为将蛋白质灵活性纳入对接算法和药物设计的手段。在本研究中，混合粗粒度方法应用于分析一个重要的酶，三磷酸异构酶的功能运动。
Elastic network model- a coarse-grained normal mode analysis- is widely used to investigate the functionally important collective motions of proteins and their complexes. Mixed coarse-graining approach has been recently introduced to the elastic network model, so that the protein's native conformation can be modeled with regions of low and high resolution. In the mixed resolution model, each node of the elastic network may represent either a single atom (high-resolution) or a residue (low-resolution), and close-neighboring nodes are connected by harmonic springs. Here, the high-resolution parts constitute the interesting parts of the protein, such as the active site, while the rest of the structure is retained at lower resolution. By performing normal mode analysis of the resulting network, the collective dynamics (low-frequency modes) and consequent conformational changes can be analyzed even for supramolecular assemblages with reasonable computational efficiency, which may serve as a means of incorporating protein flexibility into docking algorithms and drug design. In this study, the mixed coarse-graining methodology is applied to analyze the functional motions of an important enzyme, triosephosphate isomerase.