ProGuide:一种灵活的框架,用于模拟蛋白质中的全球形状重排,使用DEER衍生的距离限制
Julian D Grosskopf1, Peter Kasson2, Michael T Lerch1
1Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
ProGuide是一个新的计算框架,使用双电子共振 (DEER) 光谱数据建模蛋白质结构. 它准确地捕捉了大型结构变化,并揭示了新的结构,推进了蛋白质动态研究.
科学领域:
- 结构生物学 结构生物学
- 生物物理学的生物物理.
- 计算化学计算化学
背景情况:
- 蛋白质的结构异质性对功能至关重要,需要实验方法来可视化不同的状态.
- 双电子电子共振 (DEER) 谱学提供了自旋标签之间的远程信息,解决了蛋白质构造.
- 使用DEER距离约束器对蛋白质骨干重排的计算建模是具有挑战性的,因为旋转标签的灵活性.
研究的目的:
- 引入ProGuide,这是一个新的计算框架,用于根据DEER距离分布数据生成准确的蛋白质结构模型.
- 为了应对对蛋白质骨干重新排列和旋转标签的建模挑战,Rotameric在DEER引导建模中的灵活性.
- 将ProGuide应用于G蛋白结合受体 (GPCR),以揭示不同的构造状态.
主要方法:
- ProGuide使用代的,实验偏向的分子动力学模拟来捕捉大形状重排.
- 使用chiLife建模了Spin-label rotameric异质性,并计算了Cα变化以匹配实验DEER分布.
- 选择过程生成了一组模型,这些模型最好地汇总了DEER数据.
主要成果:
- 通过使用已公布的DEER数据,ProGuide成功生成了血管新生二型1型受体 (AT1R) 的准确结构模型.
- 这些模型揭示了不同的Gq和β-arrestin偏差构造,包括一个新的β-arrestin偏差状态.
- 获得了对微开关模式的三级重排和残留水平变化的结构洞察力.
结论:
- ProGuide有效地使用DEER衍生的距离限制来模拟蛋白质结构重排.
- 该框架在研究大型复杂蛋白质方面表现出强大和灵活性.
- 这种方法提升了生成多种蛋白质构造的完整结构模型的能力.
相关概念视频
02:26Conservation of Protein Domains Over Different Proteins
11.4K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
11.4K
02:26Conservation of Protein Domains
3.2K
3.2K
01:24Protein Organization
7.2K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
7.2K
01:49Conserved Binding Sites
4.4K
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...
4.4K
02:15Protein and Protein Structures
10.9K
10.9K
01:25Protein Folding
8.7K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.7K