DBGT-PLA:双分支图形变压器融合用于可解释的蛋白质 - 配体亲和力预测
IEEE journal of biomedical and health informatics
|January 21, 2026
概括
我们开发了一种新的框架,DBGT-PLA,用于预测蛋白质-连接体结合亲和力. 这种可解释的模型提高了准确性,并揭示了连接体相互作用是结合亲和力的关键驱动因素,有助于药物发现.
科学领域:
- 计算化学和化学信息学
- 药物的发现和开发.
- 生物信息学和计算生物学
背景情况:
- 准确的蛋白质 - 配体结合亲和力预测对于高效的药物发现至关重要.
- 现有的计算方法在同时捕获本地原子细节和全球上下文信息方面面临挑战.
研究的目的:
- 引入可解释的双分支图形转换器框架用于蛋白质 - 连接物亲和力预测 (DBGT-PLA).
- 加强当地的原子相互作用和蛋白质 - 连接体系统中的全球上下文依赖性的联合建模.
- 为合理的药物优化提供对结合亲和力决定因素的定量见解.
主要方法:
- 一个新的双分支架构,集成图形神经网络 (GNN) 与稳定性增强的变压器.
- 一个有门的残留学习 (GRL) 融合模块,用于图形拓和变压器上下文的自适应集成.
- 一个边缘级的沙普利归因框架,用于量化蛋白质-连接体图中特定相互作用的贡献.
主要成果:
- 在一个基准数据集上,DBGT-PLA实现了根平均平方误差 (RMSE) 的显著减少18.3%.
- 该模型在蛋白质 - 配体结合亲缘关系预测方面表现优于现有的最先进方法.
- 可解释性模块确定了基于联体的特征作为亲和力预测的主导贡献者 (近70%).
结论:
- DBGT-PLA为蛋白质-连接体结合亲和性预测提供了更好的准确性和可解释性.
- 该框架为管理结合亲和力的分子相互作用提供了有价值的定量见解.
- 这种方法可以指导更有效和更合理的药物设计策略.
相关概念视频
Tagging and Fusion Proteins
8.4K
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
8.4K
Metal-Ligand Bonds
24.1K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
24.1K
Affinity and Avidity
38.6K
Overview
38.6K
Ligand Binding Sites
14.9K
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...
14.9K
Ligand Binding and Linkage
5.5K
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...
5.5K
Nuclear Fusion
33.7K
The process of converting very light nuclei into heavier nuclei is also accompanied by the conversion of mass into large amounts of energy, a process called fusion. The principal source of energy in the sun is a net fusion reaction in which four hydrogen nuclei fuse and ultimately produce one helium nucleus and two positrons.
A helium nucleus has a mass that is 0.7% less than that of four hydrogen nuclei; this lost mass is converted into energy during the fusion. This reaction produces about...
A helium nucleus has a mass that is 0.7% less than that of four hydrogen nuclei; this lost mass is converted into energy during the fusion. This reaction produces about...
33.7K


