Investigation and prediction of the severity of p53 mutants using parameters from structural calculations.
Investigation and prediction of the severity of p53 mutants using parameters from structural calculations.
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DOI：
10.1111/j.1742-4658.2009.07124.x
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Persson B
中科院分区：
文献类型：
--
作者：
Carlsson J;Soussi T;Persson B
已经开发出一种方法来预测p53抑癌基因突变的影响。新方法使用了新的参数，并结合了先前建立的参数。最重要的参数是用分子模型计算的突变结构的稳定性。对于每个突变体，报告了严重程度评分，可用于将其分类为有害和无害。同时考虑了结构特征和层序属性。该方法对所有突变的预测准确率为77%，对影响WAF1启动子结合的乳腺癌突变的预测准确率为88%。与以前的方法相比，使用相同的数据集，我们的方法显然执行得更好。作为为每个突变计算的严重性分数的结果，可以获得关于P53的有价值的知识，P53是一种被认为与超过50%的人类癌症有关的蛋白质。
A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important parameter is the stability measure of the mutated structure calculated using molecular modelling. For each mutant, a severity score is reported, which can be used for classification into deleterious and nondeleterious. Both structural features and sequence properties are taken into account. The method has a prediction accuracy of 77% on all mutants and 88% on breast cancer mutations affecting WAF1 promoter binding. When compared with earlier methods, using the same dataset, our method clearly performs better. As a result of the severity score calculated for every mutant, valuable knowledge can be gained regarding p53, a protein that is believed to be involved in over 50% of all human cancers.
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