潜在的内分泌干扰化学物质与全人蛋白质组的相互作用,由AlphaFold2使用In Silico方法预测
Fan Zhang1, Yawen Tian1, Yitao Pan1
1State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China.
Environmental science & technology
|September 11, 2024
概括
这项研究使用人工智能预测了1200多种环境污染物如何与人体蛋白质结合,确定了内分泌破坏性化学物质的关键相互作用和毒性途径.
科学领域:
- 环境毒理学环境毒理学
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 蛋白质结合是环境污染物毒性的关键机制.
- 以前的研究受到3D蛋白质结构可用性和污染物范围的限制.
研究的目的:
- 使用先进的计算方法探索人类蛋白质和环境污染物之间的相互作用.
- 识别潜在的内分泌干扰化学物质及其结合性标.
- 描述绑定模式并告知不良结果路径 (AOP) 模型.
主要方法:
- 利用AlphaFold2进行精确的3D人类蛋白质结构.
- 对超过6000万种蛋白质污染物相互作用进行了分子对接.
- 分析了使用缩小尺寸和集群的绑定数据.
主要成果:
- 确定了1.2%的对接结果的高结合相互作用 (得分< -7).
- 单细胞到巨细胞分化因子2 (MMD2) 显示了最高的污染物相互作用 (526).
- 对于诸如 perfluoroalkyl 和 polyfluoroalkyl 物质 (PFAS) 和酸盐等污染物,出现了不同的蛋白质概况.
- 富含充电残留物和β片含量的结合口袋有利于PFAS结合.
结论:
- 提供了污染物-蛋白质相互作用和潜在毒性途径的全面地图.
- 突出了特定的化学类和蛋白质结构特征,涉及到结合.
- 为开发和扩展基于AOP的毒性模型提供了见解.
更多相关视频
16:02Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
2.6K
04:14Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
784
相关概念视频
Protein-protein Interfaces
12.5K
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...
12.5K
Protein Networks
3.9K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
3.9K
Target Cell Response to Hormones
3.0K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
3.0K
