用自由能量计算和机器学习方法对蛋白质-蛋白质结合亲和力进行分类
Emma Goulard Coderc de Lacam1, Benoît Roux2,3, Christophe Chipot1,2,4,5
1Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche no. 7019, Université de Lorraine, B.P. 70239, 54506 Vandœuvre-lès-Nancy Cedex, France.
Journal of chemical information and modeling
|January 25, 2024
概括
研究人员使用计算方法来理解为什么果中的某些蛋白质相互作用结合得很强,而另一些则结合得很弱. 他们确定了关键的分子细节,并开发了一个机器学习模型来预测跨物种的结合亲和力.
科学领域:
- 神经科学是一个神经科学.
- 计算生物学 计算生物学
- 生物物理学的生物物理.
背景情况:
- 果,Drosophila melanogaster的神经线路对大脑功能至关重要.
- Dpr-DIP互动组与神经元连接有关,但只有部分复合体表现出强烈的结合亲和力.
研究的目的:
- 为了阐明Dpr-DIP互动组内的差异性结合亲缘关系的残留水平分子基础.
- 开发和验证蛋白质与蛋白质结合亲和力的预测计算模型.
主要方法:
- 使用统计力学模拟和几何路线进行有约束力的自由能量计算.
- 机器学习算法的应用,包括线性差别分析和随机森林.
- 对类似蛋白质家族的预测模型进行跨物种验证.
主要成果:
- 对两个复合物的实验性结合亲和力的准确复制.
- 预测两个低亲缘关系复合物的结合自由能量,并识别关键残留物.
- 机器学习模型在区分强 binders 和弱 binders 方面实现了高精度 (0.99).
- 模型在13种不同的物种中展示了强度和可靠性.
结论:
- 计算方法,结合基于物理的模拟和机器学习,可以有效地解读蛋白质-蛋白质结合亲和力的分子决定因素.
- 开发的机器学习模型为互动组分析和关键结合残留物识别提供了一个广泛适用的工具.
- 这些发现突出了跨物种预测蛋白相互作用的潜力,推动了我们对保存生物机制的理解.
相关概念视频
01:22Protein-Drug Binding: Determination Methods
184
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
184
02:18The Equilibrium Binding Constant and Binding Strength
12.9K
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:
12.9K
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
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
02:40Ligand Binding Sites
12.8K
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...
12.8K
02:26Protein Networks
4.0K
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,...
4.0K