...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Unravelling the binding mechanism and protein stability of human serum albumin while interacting with nefopam analogues: a biophysical and insilico approach
【24h】

Unravelling the binding mechanism and protein stability of human serum albumin while interacting with nefopam analogues: a biophysical and insilico approach

机译：揭开人血清白蛋白的结合机制和蛋白质稳定性，同时与Nefopam类似物相互作用：生物物理和Insilico方法

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

In this study, molecular binding affinity was investigated for Nefopam analogues (NFs), a functionalized benzoxazocine, with human serum albumin (HSA), a major transport protein in the blood. Its binding affinity and concomitant changes in its conformation, binding site and simulations were also studied. Fluorescence data revealed that the fluorescence quenching of HSA upon binding of NFs analogues is based on a static mechanism. The three analogues of NFs binding constants (K-A) are in the order of NF3>NF2>NF1 with values of 1.53 +/-.057x10(4), 2.16 +/-.071x10(4) and 3.6 +/-.102x10(5)M(-1), respectively. Concurrently, thermodynamic parameters indicate that the binding process was spontaneous, and the complexes were stabilized mostly by hydrophobic interactions, except for NF2 has one hydrogen bond stabilizes it along with hydrophobic interactions. Circular dichroism (CD) studies revealed that there is a decrease in -helix with an increase in -sheets and random coils signifying partial unfolding of the protein upon binding of NFs, which might be due to the formation of NFs-HSA complexes. Further, molecular docking studies showed that NF1, NF2 and NF3 bound to subdomains IIIA, IB and IIA through hydrophobic interactions. However, NF1 have additionally formed a single hydrogen bond with LYS 413. Furthermore, molecular simulations unveiled that NFs binding was in support with the structural perturbation observed in CD, which is evident from the root mean square deviation and R-g fluctuations. We hope our insights will provide ample scope for engineering new drugs based on the resemblances with NFs for enhanced efficacy with HSA.
机译：在该研究中，研究了奈福泮类似物（NFS），官能化的苯并恶唑胺，具有人血清白蛋白（HSA），血液中的主要运输蛋白质的分子结合亲和力。还研究了其构象，结合位点和模拟的结合亲和力和伴随变化。荧光数据显示，在NFS类似物结合后HSA的荧光猝灭基于静态机制。 NFS结合常数（KA）的三个类似物为NF3> NF2> NF1的顺序，值为1.53 +/-。057x10（4），2.16 +/-。071x10（4）和3.6 +/-。102x10（ 5）M（-1）分别。同时，热力学参数表明结合过程是自发的，并且除了NF 2具有疏水键外，复合物主要通过疏水相互作用稳定，并且具有疏水性相互作用。圆形二中间（CD）研究表明， - 在蛋白质和随机线圈上增加了蛋白质的结合时蛋白质展开的随机线圈，这可能是由于NFS-HSA复合物的形成。此外，分子对接研究表明，通过疏水相互作用，NF1，NF2和NF3与亚域，IB和IIA结合。然而，NF1另外形成了具有Lys 413的单个氢键。此外，揭开了NFS结合的分子模拟在CD中观察到的结构扰动，这是从根系平方偏差和R-G波动中明显看出。我们希望我们的见解将根据与HSA的增强疗效增强效果，为工程新药物提供充足的工程新药物。

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