Low-resolution structures of proteins in solution retrieved from X-ray scattering with a genetic algorithm
Low-resolution structures of proteins in solution retrieved from X-ray scattering with a genetic algorithm
复制标题
DOI：
10.1016/s0006-3495(98)77984-6
复制
发表时间：
1998-06-01
影响因子：
3.4
通讯作者：
Andreu, JM
中科院分区：
文献类型：
--
作者：
Chacón, P;Morán, F;Andreu, JM
用一种新的方法对小角x射线溶液散射（SAXS）进行了分析，以检索符合散射剖面的收敛模型结构。定义了包含问题对象的数百个珠子的任意六边形填料。采用遗传算法，有效地搜索构型空间并演化出最适合的头部模型，而不是试图为所有可能的质量分布计算Debye公式。不同算法运行的模型具有相似或相同的结构。在连续的细化周期中，通过减小头半径和减小搜索空间来提高建模分辨率。该方法已经用x射线晶体结构计算的蛋白质SAXS （0.001 < S < 0.06埃（-1））进行了测试，并在剖面中加入了噪声。所得到的模型与已知结构的体积和旋转半径非常接近，并忠实地再现了每个结构的尺寸和形状。这包括发现溶菌酶的活性位点空腔，γ -结晶蛋白的双叶状结构，β - b2-结晶蛋白中由一个柄连接的两个结构域，以及胰腺核糖核酸酶抑制剂的马蹄形。溶菌酶的低分辨率溶液结构由其实验SAXS谱（0.003 < S < 0.03埃（-1））直接模拟。该模型描述溶菌酶的大小和形状的分辨率的测量。该方法可应用于其他蛋白质，区域运动分析，溶液和晶体结构的比较，以及大型大分子组装。
Small-angle x-ray solution scattering (SAXS) is analyzed with a new method to retrieve convergent model structures that fit the scattering profiles. An arbitrary hexagonal packing of several hundred beads containing the problem object is defined. Instead of attempting to compute the Debye formula for all of the possible mass distributions, a genetic algorithm is employed that efficiently searches the configurational space and evolves best-fit bead models. Models from different runs of the algorithm have similar or identical structures. The modeling resolution is increased by reducing the bead radius together with the search space in successive cycles of refinement. The method has been tested with protein SAXS (0.001 < S < 0.06 Angstrom(-1)) calculated from x-ray crystal structures, adding noise to the profiles. The models obtained closely approach the volumes and radii of gyration of the known structures, and faithfully reproduce the dimensions and shape of each of them. This includes finding the active site cavity of lysozyme, the bilobed structure of gamma-crystallin, two domains connected by a stalk in beta b2-crystallin, and the horseshoe shape of pancreatic ribonuclease inhibitor. The low-resolution solution structure of lysozyme has been directly modeled from its experimental SAXS profile (0.003 < S < 0.03 Angstrom(-1)). The model describes lysozyme size and shape to the resolution of the measurement. The method may be applied to other proteins, to the analysis of domain movements, to the comparison of solution and crystal structures, as well as to large macromolecular assemblies.