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相关概念视频

Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
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相关实验视频

Updated: Jun 9, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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提高对接和虚拟选性能,使用AlphaFold2多态模拟用于激酶.

Jinung Song1, Junsu Ha2, Juyong Lee1,2,3

  • 1College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

Scientific reports
|October 25, 2024
PubMed
概括
此摘要是机器生成的。

针对AlphaFold2 (AF2) 激酶结构的多态建模 (MSM) 通过克服结构偏差来改善药物发现. 这种方法增强了虚拟查,更有效地识别了各种类激酶抑制剂.

关键词:
在AlphaFold2中,我们使用了AlphaFold2.整体选检查 整体选基因酶激酶的使用方法多状态建模多状态建模蛋白质 - 合物对接基于结构的虚拟选.

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科学领域:

  • 计算化学是一种计算化学.
  • 结构生物学是结构生物学.
  • 药物发现 药物发现

背景情况:

  • 基于结构的虚拟查 (SBVS) 在药物发现中至关重要,但受蛋白质结构变异的限制.
  • 酶药物发现面临挑战,原因是活性部位的形状变化和对DFGin状态结构的偏见.

研究的目的:

  • 为AlphaFold2 (AF2) 激酶结构引入一个多态建模 (MSM) 协议.
  • 通过发现多种抑制剂支架来解决SBVS中的结构偏差.

主要方法:

  • 开发并应用了使用特定状态模板的AF2激酶结构的MSM协议.
  • 通过综合SBVS进行了全面的基准评估模型质量,绑定姿势预测和打击化合物识别.

主要成果:

  • 与标准AF2模型相比,MSM模型的结构准确性与标准AF2模型相比可以比较或提高.
  • 观察到增强的结合姿势预测准确性和更好地捕捉酶-联结体相互作用.
  • 在虚拟选中,MSM在标准AF2和AF3建模中始终表现优于MSM,识别了更多多样化的打击化合物.

结论:

  • 在酶向药物发现中,MSM为结构偏差提供了一个有希望的解决方案.
  • 该协议可以通过促进化学多样化的抑制剂的识别来扩大激酶抑制剂发现的范围.