IRIS:一种基于机器学习的姿势重新排名工具,用于RNA-连接器对接
Jason Andrew Amburn1, Shalini J Rukmani2,3, Jerry M Parks2,4
1Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee 37996, United States.
ACS omega
|March 16, 2026
概括
智能RNA交互得分器 (IRIS) 提高了RNA - 连接体对接位置排名. 这种机器学习模型提高了针对RNA分子的基于结构的药物发现的准确性.
科学领域:
- 计算化学是一种计算化学.
- 结构生物学是结构生物学.
- 药物发现 药物发现
背景情况:
- RNA分子在细胞过程和疾病中至关重要,使它们成为关键的治疗点.
- 通过计算对接来准确预测RNA-ligand复杂的3D结构,对于合理的药物设计至关重要.
- 由于RNA的灵活性和充电的骨干,RNA-连接对接具有挑战性,并且像rDock这样的现有工具在准确的姿势排名方面扎.
研究的目的:
- 开发和验证智能RNA交互得分器 (IRIS),这是一种新的机器学习模型,用于增强RNA-合体对接姿势排名.
- 为了提高在药物发现管道中识别RNA目标的近原生配体姿势的准确性.
主要方法:
- 开发了IRIS,一种使用物理化学和基于相互作用的特征的回归模型.
- 训练有素的IRIS使用了基于ML的RNA对接工具 (608个结构) 可用的实验性核酸-连接体复合物的最大数据集.
- 将IRIS与rDock程序集成在一起,以重新排序rDock生成的连接物姿势.
主要成果:
- 与单独使用rDock分数相比,IRIS显著提高了rDock的RNA-连接体姿势排名准确性.
- 在使用最好的rDock协议时,IRIS将近本地姿势在前五名中的成功率从64.6%提高到78.0%.
- IRIS提高了排名最高的姿势准确性,正确的姿势在59.8%的案例中排名第一,高于rDock的42.7%.
结论:
- IRIS有效地提高了RNA-连接体对接姿势排名的准确性.
- 该模型可以无地集成到现有的对接工作流程中,以改善RNA向药物发现.
- 对于针对RNA标的基于结构的抑制剂设计,IRIS提供了显著的进步.
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
1.3K
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
2.6K
相关概念视频
02:40Ligand Binding Sites
15.7K
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...
15.7K
02:40Ligand Binding Sites
9.0K
9.0K
01:49Conserved Binding Sites
5.3K
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...
5.3K
01:29Protein Folding Quality Check in the RER
5.4K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
5.4K