Domain Motion Enhanced (DoME) Model for Efficient Conformational Sampling of Multidomain Proteins
Domain Motion Enhanced (DoME) Model for Efficient Conformational Sampling of Multidomain Proteins
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DOI：
10.1021/acs.jpcb.5b07668
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发表时间：
2015-11-19
影响因子：
3.3
通讯作者：
Sugita, Yuji
中科院分区：
文献类型：
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作者：
Kobayashi, Chigusa;Matsunaga, Yasuhiro;Sugita, Yuji
由于时间尺度较慢，使用全原子分子动力学（MD）很难模拟多域蛋白质的大构象变化。我们证明，对基于结构的粗粒度 (CG) 模型进行简单修改可以对这些蛋白质进行稳定且高效的 MD 模拟。运动树是描述蛋白质中两个结构之间构象变化的树图，提供有关刚性结构单元（域）和域运动幅度的信息。在我们的新 CG 模型中，我们称之为 DoME（域运动增强）模型，域间相互作用被定义为与图中域运动的幅度成反比，而域内相互作用保持不变。我们将 DoME 模型与 Go 模型结合应用来模拟腺苷酸激酶 (AdK)。 DoME-Go模拟的结果与10μs的全原子MD模拟以及已知的实验数据一致。与传统的 Go 模型不同，DoME-Go 模型针对温度变化产生稳定的模拟轨迹，并且尽管域刚性，但构象转变很容易采样。显然，结构域及其界面的识别是多结构域蛋白质 CG 建模的有用方法。
Large conformational changes of multidomain proteins are difficult to simulate using all-atom molecular dynamics (MD) due to the slow time scale. We show that a simple modification of the structure-based coarse-grained (CG) model enables a stable and efficient MD simulation of those proteins. Motion Tree, a tree diagram that describes conformational changes between two structures in a protein, provides information on rigid structural units (domains) and the magnitudes of domain motions. In our new CG model, which we call the DoME (domain motion enhanced) model, interdomain interactions are defined as being inversely proportional to the magnitude of the domain motions in the diagram, whereas intradomain interactions are kept constant. We applied the DoME model in combination with the Go model to simulations of adenylate kinase (AdK). The results of the DoME-Go simulation are consistent with an all-atom MD simulation for 10 mu s as well as known experimental data. Unlike the conventional Go model, the DoME-Go model yields stable simulation trajectories against temperature changes and conformational transitions are easily sampled despite domain rigidity. Evidently, identification of domains and their interfaces is useful approach for CG modeling of multidomain proteins.