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HIGH PERFORMANCE METHOD TO FUNCTIONALLY CLASSIFY IDENTIFIED PROTEINS USING A GENOMIC APPROACH.

机译:使用基因组方法对蛋白质进行功能分类的高性能方法。

摘要

Method for determining at least one biological function of a target protein, said method comprising: (a) selecting a multiplicity of different molecules for their ability to modify the stability of said target protein, in which the modification of the unfolding curve of said target protein by a molecule indicates that the molecule binds to said target protein, said selection step comprising: (a1) contacting said target protein with one or more of said multiplicity of different molecules in each of a multiplicity of containers; (a2) treating said target protein in each of said multiplicity of containers to make the protein unfold; (a3) measuring in each of said containers a physical change associated with the deployment of said target protein; (a4) generate a deployment curve for said target protein for each of said containers; (a5) compare each of said unfolding curves in step (a4) with the unfolding curve obtained for said protein in the absence of any of said multiplicity of different molecules; and (a6) determining whether any of said multiplicity of different molecules modifies the stability of said protein, in which a change in stability is indicated by a shift in the unfolding curve; and (b) in which a change in stability is indicated in step (a6), determining at least one biological function of said target protein by: (b1) generating a first list of molecules that modify the unfolding curve of said target protein; and (b2) the comparison of said first list of molecules with at least a second list of molecules, in which the molecules in said second list are known to modify the unfolding curve of a group of proteins that share biological function; and (b3) the determination of whether any molecule in said first list is included in said second list, thereby determining at least one biological function of the target protein.
机译:用于确定靶蛋白的至少一种生物学功能的方法,所述方法包括:(a)针对其修饰所述靶蛋白的稳定性的能力选择多种不同的分子,其中所述靶蛋白的展开曲线的修饰“分子”表示该分子与所述靶蛋白结合,所述选择步骤包括:(a1)使所述靶蛋白与多个容器中的每个容器中的一个或多个所述多个不同分子接触; (a2)在所述多个容器的每一个中处理所述靶蛋白以使蛋白展开; (a3)在每个所述容器中测量与所述靶蛋白的部署有关的物理变化; (a4)为每个所述容器产生所述靶蛋白的展开曲线; (a5)将步骤(a4)中的每个所述展开曲线与在没有所述多种不同分子的任何情况下针对所述蛋白质获得的展开曲线进行比较; (a6)确定所述多种不同分子中的任何一种是否修饰了所述蛋白质的稳定性,其中稳定性的变化通过展开曲线的移动来指示; (b)在步骤(a6)中指示稳定性的变化,通过以下步骤确定所述靶蛋白的至少一种生物学功能:(b1)产生修饰所述靶蛋白的解链曲线的分子的第一列表; (b2)将所述第一分子列表与至少第二分子列表进行比较,其中已知所述第二分子列表中的分子修饰了一组具有生物学功能的蛋白质的展开曲线; (b3)确定所述第一列表中是否包括任何分子,从而确定所述靶蛋白的至少一种生物学功能。

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