...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Beyond Affinity: Enthalpy-Entropy Factorization Unravels Complexity of a Flat Structure-Activity Relationship for Inhibition of a tRNA-Modifying Enzyme
【24h】

Beyond Affinity: Enthalpy-Entropy Factorization Unravels Complexity of a Flat Structure-Activity Relationship for Inhibition of a tRNA-Modifying Enzyme

机译：超越亲和力：熵熵分解揭示了抑制tRNA修饰酶的平面结构-活性关系的复杂性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Lead optimization focuses on binding-affinity improvement. If a flat structure-activity relationship is detected, usually optimization strategies are abolished as unattractive. Nonetheless, as affinity is composed of an enthalpic and entropic contribution, factorization of both can unravel the complexity of a flat, on first sight tedious SAR. In such cases, the binding free energy of different ligands can be rather similar, but it can factorize into enthalpy and entropy distinctly. We investigated the thermodynamic signature of two classes of lin-benzopurines binding to tRNA-guanine transglycosylase. While the differences are hardly visible in the free energy, they involve striking enthalpic and entropic changes. Analyzing thermodynamics along with structural features revealed that one ligand set binds to the protein without inducing significant changes compared to the apo structure; however, the second series provokes complex adaptation, leading to a conformation similar to the substrate-bound state. In the latter state, a cross-talk between two pockets is suggested.
机译：线索优化专注于结合亲和力的改善。如果检测到平坦的结构-活性关系，通常由于没有吸引力而取消了优化策略。但是，由于亲和力是由焓和熵的贡献组成的，因此两者的因式分解都可以揭示平视乏味的SAR的复杂性。在这种情况下，不同配体的结合自由能可能非常相似，但可以明显地分解为焓和熵。我们调查了两类与tRNA-鸟嘌呤转糖基酶结合的Lin-苯并嘌呤的热力学特征。尽管这种差异在自由能中几乎看不到，但它们涉及到惊人的焓变和熵变。分析热力学及其结构特征后发现，与载脂蛋白结构相比，一个配体组与蛋白质结合而不会引起显着变化。然而，第二系列引发了复杂的适应，导致了类似于底物结合状态的构象。在后一种状态下，建议在两个口袋之间进​​行串扰。

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