炼化自由能量工作流程用于计算蛋白质 - 配体结合亲和关系
Anna M Herz1, Tahsin Kellici2,3, Inaki Morao2
1EaStChem School of Chemistry, Joseph Black Building, University of Edinburgh, Edinburgh, UK.
Methods in molecular biology (Clifton, N.J.)
|September 13, 2023
概括
炼金术自由能源方法通过自动化复杂的模拟来简化药物发现. 不同的工作流程简化了非专家的设置,尽管直接比较仍然存在互操作性挑战.
科学领域:
- 计算化学的计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 炼金术自由能量方法有效计算相对结合的自由能量.
- 工作流自动化复杂的模拟设置,用于非专家在药物发现.
研究的目的:
- 审查和讨论各种学术和商业工作流程的炼金术自由能量计算.
- 突出跨工作流的功能,映射算法和采样方法的差异.
主要方法:
- 对炼化自由能源工作流程的审查:FEW,FESetup,FEPrepare,CHARMM-GUI,Transformato,PMX,QLigFEP,TIES,ProFESSA,PyautoFEP,BioSimSpace,FEP+,Flare,和Orion. 在这个过程中,我们可以使用这些工作流程.
- 分析工作流组件:分子定义,原子映射,拓生成,网络生成,模拟执行和结果分析.
- 考虑分子动力学 (MD) 引擎兼容性和外部图书馆的使用.
主要成果:
- 工作流程大大促进了对相对约束力的自由能源计算的自由能源模拟的设置.
- 多样化的工作流提供了不同的绘图方法,增强的采样和MD引擎集成.
- 算法和特征存在关键差异,影响适用于特定用例的适用性.
结论:
- 自动化工作流程提高了化学自由能源方法在药物发现中的可访问性和效率.
- 工作流组件之间缺乏互操作性阻碍了标准化的比较和基准测试.
- 进一步的发展应侧重于标准化,以实现更系统的评估和更广泛的采用.
更多相关视频
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
1.2K
06:50Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
1.9K
相关概念视频
02:18The Equilibrium Binding Constant and Binding Strength
13.0K
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:
13.0K
02:40Ligand Binding Sites
12.9K
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...
12.9K
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
02:04Protein-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
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