TOP-IDP-scale: A new amino acid scale measuring propensity for intrinsic disorder
TOP-IDP-scale: A new amino acid scale measuring propensity for intrinsic disorder
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DOI：
10.2174/092986608785849164
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发表时间：
2008-09-01
影响因子：
1.6
通讯作者：
Dunker, A. Keith
中科院分区：
文献类型：
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作者：
Campen, Andrew;Williams, Ryan M.;Dunker, A. Keith
内在无序的蛋白质在缺乏有序的二级和/或三级结构的情况下执行各种生物功能。为了找到氨基酸残基的一般内在性质，负责在内在无序的蛋白质中缺乏有序结构，我们调查了517个氨基酸尺度。这些尺度中的每一个都被作为一个独立的属性用于后续的分析。对于给定的属性值X，它是在连续的氨基酸串上平均的，对于具有有序段和无序段的给定数据集，可以分别为有序和无序的条件概率P（s(o)竖条X）和P（s(d)竖条X）确定X的所有可能值。条件概率P（s(o)竖条X）和P（s(d)竖条X）相对于X的图给出一对曲线。这两条曲线之间的面积除以图的总面积得到面积比值（ARV），它与两条概率曲线的分离程度成正比，因此，提供了给定属性区分有序和无序的能力的度量。由于ARV介于0和1之间，较大的ARV对应于更好地区分有序和无序。从ARV最高的尺度开始，我们应用模拟退火程序来搜索替代尺度值，并设法将ARV提高了10%以上。在这个新的TOP-IDP量表中，氨基酸的排名如下（从有序促进到无序促进）：W， F， Y， I， M， L， V， N， C， T， A， G， R， D， H， Q， K， S， E， P.一个基于web的服务器已经创建，用于应用TOP-IDP量表来预测内在无序的蛋白质（http://www.disprot.org/dev/disindex.php）。
Intrinsically disordered proteins carry out various biological functions while lacking ordered secondary and/or tertiary structure. In order to find general intrinsic properties of amino acid residues that are responsible for the absence of ordered structure in intrinsically disordered proteins we surveyed 517 amino acid scales. Each of these scales was taken as an independent attribute for the subsequent analysis. For a given attribute value X, which is averaged over a consecutive string of amino acids, and for a given data set having both ordered and disordered segments, the conditional probabilities P(s(o) vertical bar x) and P(s(d) vertical bar x) for order and disorder, respectively, can be determined for all possible values of X. Plots of the conditional probabilities P(s(o) vertical bar x) and P(s(d) vertical bar x) versus X give a pair of curves. The area between these two curves divided by the total area of the graph gives the area ratio value (ARV), which is proportional to the degree of separation of the two probability curves and, therefore, provides a measure of the given attribute's power to discriminate between order and disorder. As ARV falls between zero and one, larger ARV corresponds to the better discrimination between order and disorder. Starting from the scale with the highest ARV, we applied a simulated annealing procedure to search for alternative scale values and have managed to increase the ARV by more than 10%. The ranking of the amino acids in this new TOP-IDP scale is as follows (from order promoting to disorder promoting): W, F, Y, I, M, L, V, N, C, T, A, G, R, D, H, Q, K, S, E, P. A web-based server has been created to apply the TOP-IDP scale to predict intrinsically disordered proteins (http://www.disprot.org/dev/disindex.php).