Protein flexibility and dynamics using constraint theory
Protein flexibility and dynamics using constraint theory
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DOI：
10.1016/s1093-3263(00)00122-4
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发表时间：
2001-01-01
影响因子：
2.9
通讯作者：
Kuhn, LA
中科院分区：
文献类型：
--
作者：
Thorpe, MF;Lei, M;Kuhn, LA
提出了一种确定蛋白质中刚性军团及其柔性连接的新方法。蛋白质中的短程力被建模为约束条件，我们从图论中提出了一种新的形式主义来分析键网络中的柔性。力包括在分析中的共价键拉伸和键弯曲力，盐桥，和氢键。我们提出了一个局部函数，将能量与单个氢键联系起来，然后可以根据键强度将其包括或排除。彩色地图的刚性和灵活的区域提供了一个直接的可视化的运动的蛋白质可以耙的地方，符合这些距离的限制，我们还定义了一个灵活性指数，数量的本地密度的灵活或松软的模式，在二面角的角度，保持自由旋转，在每个灵活的区域。负柔度指数提供了刚性区域中冗余键密度的度量，该方法的一个新应用是通过在距离约束下引入自由二面角的Monte Carlo变化来模拟柔性区域可能的最大运动范围。这是使用一种方法来完成的，该方法保持了蛋白质柔性部分中由共价键和氢键形成的环的闭合，并且避免了原子之间的货车范德华重叠。我们使用HN蛋白酶的可能运动的轨迹作为例子;其运动的电影可以在http://www.pa.msu.edu/similar上看到。(C)2001年，Elsevier Science Inc.
A new approach is presented for determining the rigid legions in proteins and the flexible joints between them. The short-range forces in proteins are modeled as constraints and we rise a recently developed formalism from graph theory to analyze flexibility in the bond network. Forces included in the analysis are the covalent bond-stretching and bond-bending forces, salt bridges, and hydrogen bonds. We rise a local function to associate an energy with individual hydrogen bonds, which then can be included or excluded depending on the bond strength. Colored maps Of the rigid and flexible regions provide a direct visualization of where the motion of the protein can rake place, consistent with these distance constraints We also define a flexibility index that quantities the local density of flexible or floppy modes, in terms of the dihedral angles that remain free to rotate in each flexible region. A negative flexibility index provides a measure of the density of redundant bonds in rigid,regions.A new application of this approach is to simulate the maximal range of possible motions of the flexible regions by introducing Monte Carlo changes in the free dihedral angles, subject to the distance constraints. This is done using a method that maintains closure of the rings formed by covalent and hydrogen bonds in the flexible parts of the protein, and van der Waals overlaps between atoms are avoided. We use the locus of the possible motions of HN protease ns an example; movies of its motion can be seen at http://www.pa.msu.edu/similar to lei. (C) 2001 by Elsevier Science Inc.