Internal Normal Mode Analysis (iNMA) Applied to Protein Conformational Flexibility
Internal Normal Mode Analysis (iNMA) Applied to Protein Conformational Flexibility
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DOI：
10.1021/acs.jctc.5b00724
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发表时间：
2015-11-01
影响因子：
5.5
通讯作者：
Lavery, Richard
中科院分区：
文献类型：
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作者：
Frezza, Elisa;Lavery, Richard
我们分析了正常模式预测观察到的蛋白质构象变化的能力，特别是由蛋白质蛋白质复合物的形成引起的变化。我们表明，在内部坐标空间（ICS）中计算的法线模式可以提供更好的预测。对于大型测试集，使用 ICS 方法可以更完整地描述构象变化，并且与等效的笛卡尔坐标模式相比，低频模式更少，尽管内部坐标计算仅限于扭转角。这可以归因于这样的事实：ICS的使用扩大了沿相应特征向量的运动保持接近真实构象能量超曲面的范围。我们还表明 PaLaCe 粗粒蛋白质模型比简单的弹性网络模型表现更好。我们将 ICS 正态模式分析应用于蛋白质复合物，并通过扩展 Sunada 和 Go 的方法，[Sunada, S.;去吧，新泽西计算机。化学。 1995, 16, 328-336]，我们证明我们可以将 ICS 模式引起的笛卡尔坐标运动的准确视图与负责运动的关键残基的检测结合起来。
We analyze the capacity of normal modes to predict observed protein conformational changes, and, notably, those induced by the formation of protein protein complexes. We show that normal modes calculated in internal coordinate space (ICS) provide better predictions. For a large test set, using the ICS approach describes the conformational changes more completely, and with fewer low-frequency modes than the equivalent Cartesian coordinate modes, despite the fact that the internal coordinate calculations were restricted to torsional angles. This can be attributed to the fact that the use of ICS extends the range over which movements along the corresponding eigenvectors remain close to the true conformational energy hypersurface. We also show that the PaLaCe coarse-grain protein model performs better than a simple elastic network model. We apply ICS normal-mode analysis to protein complexes and, by extending the approach of Sunada and Go, [Sunada, S.; Go, N. J. Comput. Chem. 1995, 16, 328-336], we show that we can couple an accurate view of the Cartesian coordinate movements induced by ICS modes with the detection of the key residues responsible for the movements.