Kinetic computational alanine scanning: Application to p53 oligomerization
Kinetic computational alanine scanning: Application to p53 oligomerization
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DOI：
10.1016/j.jmb.2005.12.083
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发表时间：
2006-03-31
影响因子：
5.6
通讯作者：
Pande, VS
中科院分区：
文献类型：
--
作者：
Chong, LT;Swope, WC;Pande, VS
我们已经开发了一种新的计算丙氨酸扫描方法，涉及在高温下的系综展开动力学分析，以确定一个给定的蛋白质的稳定性是至关重要的残基。这种方法已应用于肿瘤抑制因子p53的寡聚化结构域（残基326-355）的二聚化。正如实验结果所验证的那样，我们的方法在识别有害突变方面取得了合理的成功，包括与癌症相关的突变。我们讨论了一种方法，用于确定突变的二聚过渡态的位置上的效果。(c)2005爱思唯尔有限公司保留所有权利。
We have developed a novel computational alanine scanning approach that involves analysis of ensemble unfolding kinetics at high temperature to identify residues that are critical for the stability of a given protein. This approach has been applied to dimerization of the oligomerization domain (residues 326-355) of tumor suppressor p53. As validated by experimental results, our approach has reasonable success in identifying deleterious mutations, including mutations that have been linked to cancer. We discuss a method for determining the effect of mutations on the location of the dimerization transition state. (c) 2005 Elsevier Ltd. All rights reserved.