从使用Umol的序列信息来预测蛋白质-连接体复合物的结构
Patrick Bryant1,2,3, Atharva Kelkar4, Andrea Guljas5
1Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 12, 14195, Berlin, Germany. patrick.bryant@live.com.
Nature communications
|May 28, 2024
概括
这项研究介绍了一种AI系统,用于从序列中预测灵活的蛋白质 - 连接体复杂结构. 虽然经典方法仍然优越,但人工智能为选择准确的预测和识别药物发现中的粘合剂强度提供了信心指标.
科学领域:
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
- 人工智能的人工智能
背景情况:
- 蛋白质连接对药物发现至关重要,但需要高质量的,通常是刚性的蛋白质结构.
- 由于需要实验确定蛋白质结构,现有的方法面临局限性.
研究的目的:
- 开发一种能够从氨基酸序列直接预测完全灵活,全原子蛋白质-连接体复杂结构的AI系统.
- 评估人工智能系统与经典对接方法的性能.
- 探索人工智能预测的信心指标的实用性,以评估预测准确性和绑定亲和力.
主要方法:
- 开发一种新的人工智能系统 (Umol),用于预测蛋白质 - 连接体复杂结构.
- 利用序列信息作为全原子,灵活结构预测的输入.
- 人工智能预测与已建立的经典对接方法的比较.
- 预测信心指标 (plDDT) 的应用用于过预测和区分绑定强度.
主要成果:
- 经典的对接方法,当提供晶体结构时,仍然优于开发的AI系统.
- 人工智能系统成功地从序列中预测了蛋白质-连接体复合物的完全灵活,全原子结构.
- 预测信心指标 (plDDT) 有效地帮助选择准确的预测,并区分强和弱结合因子.
结论:
- 开发的人工智能系统代表了人工智能驱动的药物发现的前进一步,通过从序列中实现灵活的结构预测.
- 需要进一步的进展,以充分捕捉使用人工智能的蛋白质-配体相互作用的复杂性.
- 人工智能系统通过提供基于信心的见解来指导实验性药物发现工作的承诺.
相关概念视频
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
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
02:04Protein-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
01:24Protein Organization
6.4K
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....
6.4K
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