接触地图驱动的对异质蛋白折叠路径的探索
Ziad Fakhoury1, Gabriele C Sosso1, Scott Habershon1
1Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
Journal of chemical theory and computation
|September 4, 2024
概括
这项研究增强了使用接触图的蛋白质折叠预测方法,以准确识别多个折叠路径. 改进的算法成功预测了复杂的蛋白质折叠机制,匹配了分子动力学模拟.
科学领域:
- 计算生物学 计算生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 蛋白质折叠途径对于理解蛋白质的功能和功能障碍至关重要.
- 预测蛋白质折叠机制,特别是那些具有多个不同的途径的蛋白质折叠机制,仍然是一个重大挑战.
- 以前的方法依赖于分子动力学 (MD) 模拟,这可能是计算密集的.
研究的目的:
- 增强以前开发的基于接触图的蛋白质折叠策略.
- 准确而稳健地预测异质蛋白折叠路径.
- 证明增强框架在具有挑战性的多重折叠途径蛋白中识别替代折叠机制的能力.
主要方法:
- 开发了一种新的拓信息度量,用于比较蛋白质接触地图.
- 重构了以图表表示的折叠路径生成过程.
- 引入了一种新的,更可靠的结构逆向映射算法,用于将接触地图转换为笛卡尔坐标.
- 在没有直接分子动力学模拟的情况下生成蛋白质折叠轨迹合集.
主要成果:
- 改进的算法显著提高了产生结构健全的折叠中间体的可靠性.
- 通过以前的战略产生的物理上无关紧要的折叠中间产品大幅减少.
- 改进的方法成功地确定了多重折叠途径蛋白质的替代折叠机制.
- 结果与直接分子动力学模拟的发现一致.
结论:
- 基于接触地图的增强战略为预测复杂的蛋白质折叠路径提供了准确而强大的方法.
- 这种方法为研究蛋白质折叠机制的分子动力学提供了一个计算效率高的替代方案.
- 该框架能够剖析复杂的折叠景观,包括具有异质二级结构元素的景观.
相关概念视频
Protein Folding
117.7K
Overview
117.7K
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
Conservation of Protein Domains Over Different Proteins
10.8K
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...
10.8K
Molecular Chaperones and Protein Folding
17.8K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
17.8K
Protein Organization
6.3K
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....
6.3K
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


