蛋白质特征工程框架用于AMPylation站点预测.
Hardik Prabhu1,2, Hrushikesh Bhosale1, Aamod Sane1
1Computing and Data Sciences, FLAME University, Pune, 412115, India.
Scientific reports
|April 15, 2024
概括
这项研究引入了一种新的计算方法,用于识别AMPylation位点,这是一个关键的蛋白质修饰. 我们的新型特征提取管道提高了机器学习模型的准确性,用于预测这些网站.
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:
- AMPylation是一种显著的翻译后修改,涉及将腺单酸盐 (AMP) 添加到氨酸和氨酸残留物中.
- 虽然人们越来越了解它的流行程度和影响,但很难在实验中确定AMPylation位点.
- 计算预测提供了一个更快的替代方案,但模型性能严重依赖于特征表示.
研究的目的:
- 开发一种新的特征提取管道,以改善AMPylation站点的计算预测.
- 评估这些新功能在用于AMPylation位点识别的机器学习模型中的有效性.
主要方法:
- 一个新的特征提取管道被设计为编码与AMPylation相关的关键属性.
- 机器学习分类器使用从提取的特征中得出的数值表示来训练.
- 使用十倍交叉验证来评估模型在区分AMPylated和非AMPylated位点方面的性能.
- 用SHapley添加式扩展 (SHAP) 来分析特征的重要性.
主要成果:
- 开发的特征提取框架在机器学习模型中证明了它的实用性.
- 性能最好的特征获得了0.58的马修斯相关系数 (MCC) 评分,准确度为0.8,AUC-ROC为0.85,F1评分为0.73.
- 分析阐明了基于使用SHAP的单图和大图计数的模型行为.
结论:
- 新型特征提取管道显著提高了AMPylation站点机器学习模型的预测性能.
- 与实验方法相比,这种方法提供了一种更有效,更准确的方法来识别AMPylation位点.
- 这些发现有助于更好地了解AMPylation,并促进对其生物作用的进一步研究.
相关概念视频
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
01:19Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
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
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