通过语言模型和几何深度学习来对蛋白质结合部位进行基因组规模的注释
Qianmu Yuan1, Chong Tian1, Yuedong Yang1
1School of Computer Science and Engineering, Sun Yat-sen University, Guangzhou, China.
eLife
|April 17, 2024
概括
GPSite使用序列和预测结构准确地识别蛋白质结合部位,推进疾病研究和药物设计. 这种方法有效地注释了数以百万计的蛋白质序列,以获得更广泛的生物学见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 识别蛋白质结合点对于了解疾病机制和设计新药至关重要.
- 现有的方法通常需要昂贵的实验结构或多个序列对齐,限制大规模应用.
- 目前的方法还没有充分利用蛋白质结构几何学.
研究的目的:
- 开发一种新的计算方法,GPSite,用于准确和高效地预测蛋白质结合点.
- 同时预测各种分子的结合残留物,包括DNA,RNA,,蛋白质,ATP,HEM和金属离子.
- 为了使蛋白质结合部位的基因组规模注释.
主要方法:
- GPSite利用了在序列嵌入和语言模型中预测的蛋白质结构上训练的多任务网络.
- 它以端到端的方式全面提取剩余和关系几何语境.
- 该方法将序列信息与预测的结构几何相结合.
主要成果:
- 在基准数据集上,GPSite显著优于现有的最先进的基于序列和基于结构的方法.
- 性能即使在不完美预测的蛋白质结构下也保持稳健.
- 该工具实现了对超过5.68万个蛋白质序列的基因组规模快速注释.
结论:
- GPSite提供了一个计算效率高,准确的解决方案,用于预测各种蛋白质结合部位.
- 它利用预测结构的能力克服了实验结构依赖性的局限性.
- 该工具通过将结合部位与分子功能和遗传变异联系起来,促进了大规模的生物发现.
相关概念视频
01:49Conserved Binding Sites
4.2K
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...
4.2K
02:40Ligand Binding Sites
12.8K
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...
12.8K
02:04Protein-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
03:36Genome Annotation and Assembly
18.8K
The genome refers to all of the genetic material in an organism. It can range from a few million base pairs in microbial cells to several billion base pairs in many eukaryotic organisms. Genome assembly refers to the process of taking the DNA sequencing data and putting it all back together in a correct order to create a close representation of the original genome. This is followed by the identification of functional elements on the newly assembled genome, a process called genome annotation.
18.8K
02:26Protein 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
00:49Ligand Binding and Linkage
4.8K
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...
4.8K