整合机器学习和蛋白质-连接体相互作用概况,以发现METTL3抑制剂
Wei-Cheng Huang1, Hsing-Pang Hsieh1, Chun-Wei Tung2,3
1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, 35053, Taiwan.
Scientific reports
|October 21, 2025
概括
研究人员开发了一种新的机器学习模型,以预测METTL3抑制剂,这对于向急性髓性白血病等癌症至关重要. 这种方法整合了合理药物设计的结构性见解.
科学领域:
- 生物化学 生化学
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- RNA的修改调节了基因表达和细胞功能.
- 瘤发生的关键酶METTL3,增强瘤转录翻译,是急性髓性白血病等癌症的治疗点.
研究的目的:
- 开发一种用于METTL3抑制生物活性的新型预测模型 (pIC50).
- 为了合理的药物设计,将机器学习与结构生物学相结合.
主要方法:
- 结合机器学习,蛋白质-连接体对接和相互作用分析.
- 编码的物理化学特性,化学指纹,以及基于对接的蛋白质 - 连接体相互作用特征 (DPLIFE).
- 使用自动堆叠组合算法和特征选择以进行模型优化 (ML3-mix-DPLIFE-FS).
主要成果:
- 在一个独立的测试组中,优化的ML3-mix-DPLIFE-FS模型实现了0.261的平均平方误差 (MSE) 和0.853的Pearson相关系数 (CC).
- 确定了8种关键残留物,这些残留物与METTL3.3相关联体相互作用.
- 预测已知抑制剂的pIC50值具有很好的准确性 (MSE=0.418,CC=0.727).
结论:
- 开发的模型有效地预测了METTL3抑制生物活性.
- 这一策略将计算预测与结构洞察整合在一起,为识别关键蛋白质-连接体相互作用提供了一种新的方法.
- 为METTL3抑制剂提供基于结构的合理药物设计.
更多相关视频
05:08Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
941
06:50Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
2.5K
相关概念视频
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
14.9K
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
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
02:26Protein 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