Jove
Visualize
联系我们
JoVE
x logofacebook logolinkedin logoyoutube logo
关于 JoVE
概览领导团队博客JoVE 帮助中心
作者
出版流程编辑委员会范围与政策同行评审常见问题投稿
图书馆员
用户评价订阅访问资源图书馆顾问委员会常见问题
研究
JoVE JournalMethods CollectionsJoVE Encyclopedia of Experiments存档
教育
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab Manual教师资源中心教师网站
使用条款与条件
隐私政策
政策

相关概念视频

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

879
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
879

您也可能阅读

相关文章

通过共同作者、期刊和引用图与本文相关的文章。

排序
Same author

CSCAN: Conformational Analysis of Macrocyclic Peptides through NMR Chemical Shifts.

Journal of chemical information and modeling·2026
Same author

Discovery of Non-prostanoid EP4 Agonists for the Treatment of Inflammatory Bowel Disease.

Journal of medicinal chemistry·2026
Same author

Structure-based pose prediction: Non-cognate docking extended to macrocyclic ligands.

Journal of computer-aided molecular design·2024
Same author

From UK-2A to florylpicoxamid: Active learning to identify a mimic of a macrocyclic natural product.

Journal of computer-aided molecular design·2024
Same author

Correction: Complex peptide macrocycle optimization: combining NMR restraints with conformational analysis to guide structure-based and ligand-based design.

Journal of computer-aided molecular design·2024
Same author

Unmasking the True Identity of Rapamycin's Minor Conformer.

Journal of natural products·2023

相关实验视频

Updated: Jul 20, 2025

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
14:44

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

Published on: December 16, 2013

9.6K

复杂的宏循环优化:将NMR限制与构造分析相结合,以指导基于结构和基于连接体的设计.

Ajay N Jain1, Alexander C Brueckner2, Christine Jorge2

  • 1Research and Development, BioPharmics LLC, Sonoma County, CA, USA. ajain@jainlab.org.

Journal of computer-aided molecular design
|August 3, 2023
PubMed
概括

优化宏环配体是非常具有挑战性的. 本研究介绍了使用NMR数据和分子相似性的计算方法来预测结合能,改善临床候选者的药物优化.

关键词:
力量 力量 力量 力量连接物菌株 - 连接物菌株宏观循环是一个宏观循环.这就是NMR的NMR.在PD-L1中.冲浪式码头 - 冲浪式码头这是一个eSim系统.

更多相关视频

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.1K
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
07:11

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

2.7K

相关实验视频

Last Updated: Jul 20, 2025

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
14:44

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

Published on: December 16, 2013

9.6K
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.1K
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
07:11

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

2.7K

科学领域:

  • 药用化学 医学化学
  • 计算化学计算化学
  • 结构生物学 结构生物学

背景情况:

  • 对宏环配体的系统优化在药物发现中提出了重大挑战.
  • 编程细胞死亡蛋白1 (PD-1) /编程死亡连接体1 (PD-L1) 途径是癌症免疫治疗的关键目标.

研究的目的:

  • 开发和验证用于宏环配体的优化的计算方法.
  • 用PD-1/PD-L1系统作为案例研究来证明这些方法的实用性.

主要方法:

  • 从核磁共振 (NMR) 数据中导出构造约束,以识别低能溶液集.
  • 采用分子对接与形状约束来预测结合联体的姿势和估计结合能量.
  • 使用基于连接体的方法与分子相似性优化来预测绑定姿势.

主要成果:

  • 两种NMR受限对接和基于联体的相似性方法都有效地优先考虑了化合物类似物.
  • 微小的连接体修饰可以不成比例地影响估计的应变能量,显著影响整体约束能量的预测.
  • 准确的宏循环的构造性搜索对于可靠的结合能量的估计至关重要.

结论:

  • 结合生物物理数据和计算方法的多学科方法提高了宏环优化的生产率.
  • 这些策略有助于从最初的化合物过渡到可行的临床候选物.