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Progress in the development of an alternative approach to macromolecular crystallization

机译：高分子结晶替代方法开发进展

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We are developing an alternate strategy for the crystallization of macromolecules that does not, like current methods, depend on the optimization of traditional variables such as pH and precipitant concentration, but is based on the hypothesis that many conventional small molecules might establish stabilizing, intermolecular,. noncovalent cross-links in crystals', and thereby promote lattice formation. Earlier experiments provided encouraging results that suggested further research was warranted (Larson, S. B.; Day, J. S.; Cudney, R.; McPherson, A. A novel strategy for the crystallization of proteins: X-ray diffraction validation. Acta Crystallogr., D: Biol. Crystallogr. 2007, 63, 310-318. McPherson, A.; Cudney, B. Searching for silver bullets: an alternative strategy for crystallizing macromolecules. J. Struct. Biol. 2006, 156, 387-406). Here we report additional, large-scale crystallization screening experiments that lend further support, though they suggest that additional mechanisms may play a positive role as well. As before, we accompanied the crystallization experiments with X-ray diffraction analyses of some of the crystals grown. A number of these showed incorporation of conventional molecules into protein crystal lattices, and further validated the underlying hypothesis. The strategy we are pursuing is essentially orthogonal to current approaches and has an objective of doubling the success rate of today.
机译：我们正在开发一种替代大分子结晶的策略，该策略不像当前方法那样依赖于传统变量（例如pH和沉淀剂浓度）的优化，而是基于许多传统小分子可能建立稳定分子间分子的假设。 。非共价交联键，从而促进晶格形成。较早的实验提供了令人鼓舞的结果，表明有必要进行进一步的研究（Larson，SB; Day，JS; Cudney，R。; McPherson，A。蛋白质结晶的新策略：X射线衍射验证。ActaCrystallogr。，D： Biol。Crystallogr。2007，63，310-318。McPherson，A .; Cudney，B.寻找银子弹：结晶大分子的另一种策略（J. Struct。Biol。2006，156，387-406）。在这里，我们报告了其他大规模结晶筛选实验，这些实验提供了进一步的支持，尽管它们表明其他机制也可能发挥积极作用。和以前一样，我们在结晶实验的同时对一些生长的晶体进行了X射线衍射分析。其中许多表明将常规分子并入蛋白质晶格，并进一步证实了潜在的假设。我们追求的策略本质上与当前方法正交，并且目标是使今天的成功率翻倍。

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