蛋白质智慧:一个工作台

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Smadbeck, J., Peterson, M. B., Khoury, G. A., Taylor, M. S., Floudas, C. A. Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules. J. Vis. Exp. (77), e50476, doi:10.3791/50476 (2013).

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Abstract

从头蛋白质设计的目的是要找到的氨基酸序列,将折叠成与特定的属性,比如,相对于天然序列的结合亲和力,激动剂或拮抗剂的行为,或稳定性的改善所希望的3维结构。蛋白质设计在于在目前的进展的药物设计和发现的中心。蛋白质设计不仅提供预测潜在的有用的药物靶标,但它也增强了我们的了解蛋白质折叠的过程中,蛋白质 - 蛋白质相互作用。定向进化的实验方法,如蛋白质设计的成功。然而,这样的方法是受限制由有限序列空间可以搜索的tractably的,的。与此相反,计算设计策略允许一个更大的集的序列,涵盖了各种各样的性能和功能的筛选。我们已开发出一系列从头计算蛋白设计METHODS能够对付蛋白质设计的几个重要领域。这些包括单体蛋白质的设计,增加了稳定性和复合物的结合亲和力增加。

为了更广泛的传播这些方法,使用我们提出蛋白质的智慧( http://www.proteinwisdom.org ),各种蛋白质设计的问题提供了一个工具,自动化的方法。提交初始化结构模板的设计过程。设计的第一阶段是一个优化序列选择阶段,目的是提高稳定性通过序列中的空间最小化势能。选择序列,然后通过折叠特异性的舞台和亲和力阶段运行。 A等级排序的列表中的每个步骤的序列的过程中,伴随着有关的设计结构,为用户提供了全面的量化评估设计​​。在这里,我们提供了详细情况Of各自的设计方法,以及几个显着的实验通过使用一种方法,已经取得的成就。

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