Domain Motion Enhanced (DoME) Model for Efficient Conformational Sampling of Multidomain Proteins

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• 作者：Chigusa Kobayashi ; Yasuhiro Matsunaga ; Ryotaro Koike ; Motonori Ota ; Yuji Sugita
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：November 19, 2015
• 年：2015
• 卷：119
• 期：46
• 页码：14584-14593
• 全文大小：665K
• ISSN：1520-5207

文摘

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. 鈥淢otion Tree鈥? 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鈥揋o simulation are consistent with an all-atom MD simulation for 10 渭s as well as known experimental data. Unlike the conventional Go model, the DoME鈥揋o 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.