基于蛋白质预训练的大型语言模型和分数顺序卷积神经网络的蛋白质-ATP结合位点的准确预测
Mengyao Guo1, Yuhang Tu1, Jiali Yu1
1School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, 100083, China.
Scientific reports
|November 25, 2025
概括
一种新的基于大型语言模型 (LLM) 的方法,PFDCNN,只使用蛋白质序列,准确地预测蛋白质-腺三酸盐 (ATP) 结合点. 这一进步有助于药物设计和疾病治疗,改善了对蛋白质-ATP相互作用的理解.
科学领域:
- 生物化学 生物化学
- 生物信息学是一种生物信息学.
- 计算生物学 计算生物学
背景情况:
- 腺三酸盐 (ATP) 对于细胞能量至关重要. 蛋白质-ATP相互作用对生物功能至关重要,因此准确的结合部位预测对于药物设计和疾病研究至关重要.
- 目前用于预测蛋白质-ATP结合位点的方法往往不灵活,需要复杂的特征提取,并可能丢失序列信息.
研究的目的:
- 开发一种新,准确和高效的模型,仅使用蛋白序列信息来预测蛋白质-ATP结合位点.
- 通过整合大型语言模型 (LLM) 和深层卷积神经网络来克服现有方法的局限性.
主要方法:
- 开发了一种基于大型语言模型 (LLM) 的新型模型,即预训练的分数顺序深卷积神经网络 (PFDCNN).
- 该模型利用由预训练的蛋白质LLM提取的序列信息,并使用具有分数顺序反向传播的深 convolutional 神经网络.
- 使用修改后的损失函数来解决数据不平衡问题.
主要成果:
- 该PFDCNN模型在蛋白质-ATP结合部位数据集上表现出卓越的概括能力.
- 该模型在两个基准数据集上实现了高精度 (0.99和0.984) 和AUC值 (0.965和0.941).
- 性能超过了大多数现有的蛋白质结合部位预测模型.
结论:
- 根据序列数据,PFDCNN模型在准确高效地预测蛋白质-ATP结合位点方面取得了重大进展.
- 这种方法有望通过提高对蛋白质-ATP相互作用的理解来改善疾病预防,诊断,治疗和药物设计.
相关概念视频
01:49Conserved Binding Sites
5.0K
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...
5.0K
02:04Protein-protein Interfaces
14.4K
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...
14.4K
02:40Ligand Binding Sites
14.8K
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...
14.8K
02:26Protein Networks
4.5K
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,...
4.5K
01:24Protein Organization
9.0K
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....
9.0K
02:07Improving Translational Accuracy
14.0K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
14.0K