Molecular dynamics studies on Mdm2 complexes: An analysis of the inhibitor influence
Molecular dynamics studies on Mdm2 complexes: An analysis of the inhibitor influence
复制标题
DOI：
10.1016/j.bbrc.2012.06.138
复制
发表时间：
2012-07-27
影响因子：
3.1
通讯作者：
Lauria, Antonino
中科院分区：
文献类型：
--
作者：
Almerico, Anna Maria;Tutone, Marco;Lauria, Antonino
p53是一种强有力的抗肿瘤分子，在癌症中经常因突变或缺失而失活。然而，一半的人类肿瘤表达野生型p53，其激活，通过拮抗其负调节Mdm 2，可能提供一个新的治疗方案的战略。在这项工作中，我们提出了一个分子动力学研究Mdm 2结构结合到两个不同的已知抑制剂，目的是调查之间的结构转换apo-Mdm 2和Mdm 2-抑制剂复合物。我们试图获得关于结合苯二氮卓类衍生物抑制剂的已知nutlin和载脂蛋白形式的构象变化的信息。的构象变化改变的大小的裂缝，主要是在连接器区域，这表明Mdm 2的整体动态性质是相关的动态运动在这些地区。(C)2012 Elsevier Inc. All rights reserved.
p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and were mainly in the linker regions, suggesting that the overall dynamic nature of Mdm2 is related to dynamic movements in these regions. (C) 2012 Elsevier Inc. All rights reserved.