在GRP78-CRIPTO结合部位的in silico预测,以改善质母细胞瘤的治疗向
Mahmoud E Rashwan1, Mahrous R Ahmed2, Abdo A Elfiky3
1Physics Department, Faculty of Science, Sohag University, Sohag, 82524, Egypt. mahmoud.ezz@science.sohag.edu.eg.
Scientific reports
|May 13, 2025
概括
这项研究确定了葡萄糖调节蛋白78 (GRP78) 和CRIPTO蛋白之间的稳定结合点,这对多种质母细胞瘤 (GBM) 瘤增殖至关重要. 了解这些相互作用为中枢神经系统瘤提供了潜在的治疗点.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 在瘤学瘤学.
背景情况:
- 多形质母细胞瘤 (GBM) 是一种具有攻击性的中枢神经系统 (CNS) 瘤.
- 在GBM中观察到过度表达葡萄糖调节蛋白78 (GRP78) 和CRIPTO.
- 之前报道的GRP78和CRIPTO之间的复合体激活了信号通路,促进了瘤的扩散.
研究的目的:
- 为了研究GRP78和CRIPTO之间的分子相互作用和结合点.
- 阐明GRP78 SBDβ和CRIPTO CFC域之间复合形成的机制.
主要方法:
- 利用计算生物物理学和生物信息学工具.
- 采用蛋白质-蛋白质对接 (Haddock 网络服务器) 来预测绑定区域.
- 进行了分子动力学模拟 (MDS) 和MMGBSA计算,以评估复杂的稳定性和结合能.
主要成果:
- 确定了GRP78 SBDβ和CRIPTO CFC域之间的四个潜在的绑定区域.
- 模拟证实了这些复合物的稳定性,结合的自由能量在-15.07~126.26 kcal/mol之间.
- 建议使用特定的结合点来调解GRP78和CRIPTO之间的稳定相互作用.
结论:
- GRP78 SBDβ稳定地与CRIPTO CFC域联系在一起.
- 已识别的结合点对于GRP78-CRIPTO复合体的形成至关重要.
- 这些发现提供了对GBM病原体和针对GRP78-CRIPTO相互作用的潜在治疗策略的见解.
更多相关视频
05:29A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
2.7K
06:32Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
7.8K
相关概念视频
02:04Protein-protein Interfaces
12.4K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.4K
02:40Ligand Binding Sites
12.6K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.6K
01:49Conserved Binding Sites
4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K