CorrEA:一个网络服务器,用于优化计算的能量和活动之间的相关性在联体受体系统考虑多个结合点构造
Sergio Alfaro1, Fabián González-Norambuena1, José Luis Velázquez-Libera1
1Centro de Bioinformática, Simulación y Modelado, Facultad de Ingeniería, Universidad de Talca, 1 Poniente No. 1141, Casilla 721, Talca 3460000, Chile.
Journal of chemical information and modeling
|June 23, 2025
概括
这项研究介绍了CorrEA,这是一款新的Web服务器,通过结合蛋白质灵活性来提高分子对接的准确性. CorrEA增强了计算的结合能和用于药物发现的实验活动之间的相关性.
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:
- 分子对接对于预测受体-连接体相互作用和指导药物设计至关重要.
- 当前的对接方法往往产生不可靠的能量值,限制了它们在将计算结果与实验生物活动相关联的使用.
- 蛋白质的灵活性被认为是更准确的对接解决方案的关键因素.
研究的目的:
- 介绍CorrEA,一个新的Web服务器,通过结合蛋白质灵活性来解决传统分子对接的局限性.
- 提供一种方法来改善计算的对接能量和实验生物活动之间的相关性.
- 为研究人员提供一个工具,以便更好地了解替代剂对连接体亲和力的作用.
主要方法:
- 用户生成多个受体构造,具有结合点变异性.
- 连带序列与这些构造交叉对接.
- 在CorrEA中,使用基因算法 (GA) 选择代表性联体-蛋白质复合体.
- GA优化了对接能量和实验活动之间的相关性.
主要成果:
- CorrEA成功地识别了结合体-蛋白对,这些对产生了计算值和实验值之间的最高相关性.
- 与标准对接方法相比,该方法在预测结合亲和度方面表现出更好的准确性.
- 在各种案例中进行了测试,CorrEA证明了其在药物发现研究中的实用性.
结论:
- 通过考虑蛋白质的灵活性,CorrEA为分子对接提供了一种创新的方法.
- 网络服务器提高了对接能源预测的可靠性,用于结构-活动关系研究.
- CorrEA是推进计算药物发现和优化的一个有价值的工具.
相关概念视频
02:40Ligand Binding Sites
13.5K
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...
13.5K
02:18The Equilibrium Binding Constant and Binding Strength
13.9K
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:
13.9K
00:49Ligand Binding and Linkage
4.9K
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...
4.9K
01:49Conserved Binding Sites
4.4K
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...
4.4K
02:04Protein-protein Interfaces
13.7K
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...
13.7K
01:58Cooperative Allosteric Transitions
2.4K
2.4K