Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.
Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.
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DOI：
10.1371/journal.pone.0101123
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Charbonneau P
中科院分区：
文献类型：
--
作者：
Fusco D;Barnum TJ;Bruno AE;Luft JR;Snell EH;Mukherjee S;Charbonneau P
X射线晶体学是获得生物大分子原子尺度信息的主要方法。尽管这项技术取得了成功，但获得良好的衍射晶体仍然严重限制了从蛋白质到结构的研究。在实践中，结晶过程是通过知识知情主义进行的。更好的物理化学理解仍然难以捉摸，因为涉及大量的变量，因此很少有指导可用于系统地确定促进结晶的溶液条件。为了帮助确定大分子性质与其结晶倾向之间的关系，我们对由Northeast Structural Genomics Consortium提供的182种蛋白质的样本进行了统计模型训练。高斯过程捕捉线性统计模型无法捕捉的趋势，区分了驱动结晶的两种主要物理化学机制。一种的特征是侧链熵水平较低，并已在文献中广泛报道。另一个识别特定的静电相互作用，以前没有在结晶的上下文中描述。由于两种不同的机制的证据可以收集晶体接触和溶液条件导致成功的结晶，该模型提供了未来的途径，优化结晶屏幕的基础上部分结构信息。因此，结晶数据的可用性加上通过最先进的统计模型分析的结构结果可能会引导大分子结晶走向更合理的基础。
X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.
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DOI：
10.1107/s090744491000644x
发表时间：
2010-05-01
影响因子：
2.2
作者：
Derewenda, Zygmunt S.
通讯作者：
Derewenda, Zygmunt S.
影响因子：
3.4
作者：
Fusco D;Headd JJ;De Simone A;Wang J;Charbonneau P
通讯作者：
Charbonneau P
DOI：
10.1002/prot.340230413
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Janin, J;Rodier, F
通讯作者：
Rodier, F
影响因子：
5.8
作者：
Chen, L;Oughtred, R;Westbrook, J
通讯作者：
Westbrook, J
影响因子：
5.7
作者：
Derewenda, ZS
通讯作者：
Derewenda, ZS