Hinsen K, Thomas A, Field M J
Laboratoire de Dynamique Moléculaire, Institut de Biologie Structurale--Jean-Piere Ebel, Grenoble, France.
Proteins. 1999 Feb 15;34(3):369-82.
We present a new approach for determining dynamical domains in large proteins, either based on a comparison of different experimental structures, or on a simplified normal mode calculation for a single conformation. In a first step, a deformation measure is evaluated for all residues in the protein; a high deformation indicates highly flexible interdomain regions. The sufficiently rigid parts of the protein are then classified into rigid domains and low-deformation interdomain regions on the basis of their global motion. We demonstrate the techniques on three proteins: citrate synthase, which has been the subject of earlier domain analyses, HIV-1 reverse transcriptase, which has a rather complex domain structure, and aspartate transcarbamylase as an example of a very large protein. These examples show that the comparison of conformations and the normal mode analysis lead to essentially the same domain identification, except for cases where the experimental conformations differ by the presence of a large ligand, such as a DNA strand. Normal mode analysis has the advantage of requiring only one experimental structure and of providing a more detailed picture of domain movements, e.g. the splitting of domains into subdomains at higher frequencies.
我们提出了一种确定大型蛋白质动力学结构域的新方法，该方法既可以基于不同实验结构的比较，也可以基于单个构象的简化正常模式计算。第一步，对蛋白质中的所有残基评估一种变形量度；高变形表明结构域间区域具有高度灵活性。然后，根据蛋白质的整体运动，将其足够刚性的部分分类为刚性结构域和低变形的结构域间区域。我们在三种蛋白质上展示了这些技术：柠檬酸合酶，它是早期结构域分析的对象；HIV-1逆转录酶，其结构域结构相当复杂；天冬氨酸转氨甲酰酶，作为一种非常大的蛋白质的示例。这些例子表明，构象比较和正常模式分析会得出基本相同的结构域识别结果，但存在实验构象因存在大配体（如DNA链）而不同的情况除外。正常模式分析的优点是只需要一个实验结构，并且能提供更详细的结构域运动情况，例如在较高频率下将结构域细分为子结构域。
