• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Structural insight into inhibition of REV7 protein interaction revealed by docking, molecular dynamics and MM/PBSA studies
【24h】

Structural insight into inhibition of REV7 protein interaction revealed by docking, molecular dynamics and MM/PBSA studies

机译：对接，分子动力学和MM / PBSA研究揭示了抑制REV7蛋白相互作用的结构见解

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In mammalian cells, DNA polymerase ζ (Pol ζ) catalyzes the TLS step of ICLR. By acting simultaneously with Y-family DNA polymerase, Pol ζ completes replication of damaged DNA without removing the damage by inserting a nucleotide opposite the lesion. It has been demonstrated that Pol ζ represents a promising target for the treatment of chemotherapy-resistant tumors. The first series of small-molecule inhibitors targeting REV7/REV3L interaction have been identified recently, however, their corresponding binding mechanism is not known. Herein, we performed docking, molecular dynamics and MM/PBSA free energy calculations to study the binding mechanism of REV7 and its inhibitors. It was demonstrated that inhibitors bind to the two pockets divided by the ‘safety-belt’ structure of REV7, which was supported by the MD simulation. In addition, 2-methylfuran is an important group with an appropriate size to form the stable complex, and hydrophobic contacts were mainly responsible for stable complex formation as revealed by free energy calculation.
机译：在哺乳动物细胞中，DNA聚合酶ζ（Polζ）催化ICLR的TLS步骤。通过与Y家族DNA聚合酶同时作用，Polζ可以完成受损DNA的复制，而无需通过在病灶对侧插入一个核苷酸来消除受损。已经证明，Polζ代表了对化疗耐药性肿瘤的治疗的有希望的靶标。最近已确定了第一批靶向REV7 / REV3L相互作用的小分子抑制剂，但是，其相应的结合机制尚不清楚。在本文中，我们进行了对接，分子动力学和MM / PBSA自由能计算，以研究REV7及其抑制剂的结合机理。结果表明，抑制剂结合到两个口袋上，被REV7的“安全带”结构分开，MD模拟得到了支持。另外，2-甲基呋喃是具有合适大小以形成稳定络合物的重要基团，并且通过自由能计算表明，疏水性接触主要负责稳定络合物的形成。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号