SAAMBE-MEM:一种基于序列的方法,用于预测膜蛋白-蛋白质复合体突变时的结合自由能量变化
Prawin Rimal1, Shailesh Kumar Panday1, Wang Xu2
1Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, United States.
Bioinformatics (Oxford, England)
|September 6, 2024
概括
一种新的基于序列的方法,SAAMBE-MEM,准确地预测了突变对膜蛋白结合亲和力的效应. 这种方法通过利用基于进化的特征来优于现有方法,这对于理解蛋白质功能和疾病至关重要.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 蛋白质-蛋白质相互作用中的突变可以改变复杂的功能并导致疾病.
- 鉴于它们的丰富性,评估突变对膜蛋白结合亲和力的影响至关重要.
- 现有的预测方法通常需要结构数据,并且仅限于可溶性蛋白质.
研究的目的:
- 开发一种基于序列的新方法来预测由于突变而导致的膜蛋白-蛋白质复合体中的结合自由能量变化 (ΔΔG).
- 克服现有方法的局限性,这些方法需要结构信息,并且主要对可溶性蛋白进行训练.
主要方法:
- 开发了SAAMBE-MEM,一种使用MPAD数据库的基于序列的机器学习方法.
- 杆功能,如氨基酸指数和位置特定评分矩阵 (PSSM).
- 使用XGBoost回归算法与精心策划的数据集训练和验证模型.
主要成果:
- SAAMBE-MEM实现了0.64的皮尔森相关系数,具有最佳的PSSM相关特征.
- 该方法的性能优于在SKEMPI数据库上训练的现有方法.
- 与物理化学特征相比,基于进化的特征表现出优越的性能.
结论:
- SAAMBE-MEM提供了一种有效的基于序列的方法,用于预测对膜蛋白结合亲和力的突变效应.
- 该方法依赖于以进化为基础的特征,凸显了它们在理解这些相互作用方面的重要性.
- 通过Web服务器和独立代码访问SAAMBE-MEM.
更多相关视频
05:56Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
1.3K
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
470
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
02:18The Equilibrium Binding Constant and Binding Strength
12.8K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
12.8K