使用静电嵌入式碎片化方法精确有效地计算蛋白质-连接体相互作用能量
Yingfeng Zhang1, Wei Xia2,3, Kaifang Huang4
1Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen 518055, China.
Journal of chemical theory and computation
|January 27, 2026
概括
准确的蛋白质 - 配体结合能量的计算对于药物设计至关重要. 这项研究完善了用结合 (EE-GMFCC) 方法进行静电嵌入式通用分子分离,以实现高效准确的量子力学 (QM) 能量计算.
科学领域:
- 计算化学是一种计算化学.
- 分子建模分子建模
- 药物发现 药物发现
背景情况:
- 精确的蛋白质 - 配体结合的自由能量计算对于合理的药物设计至关重要.
- 传统的量子力学 (QM) 方法对于大型系统来说在计算上是不可接受的.
- 碎片化方法提供了一个可计算的替代方案,但需要精确的环境建模.
研究的目的:
- 介绍和完善与结合 (EE-GMFCC) 方法的静电嵌入式通用分子分离方法,特别是EE-GMFCC[P-L],用于蛋白质-联体相互作用能量计算.
- 建立一个高精度的基准数据集,用于开发和验证计算药物设计方法.
主要方法:
- 应用和完善EE-GMFCC[P-L]方法用于QM能源计算.
- 系统地调查方法参数:连接子电荷,限制方案和基础集合.
- 对21个蛋白质-连接体系统的基准集的相互作用能量的计算.
主要成果:
- EE-GMFCC[P-L]方法通过将蛋白质点电荷场中的碎片能量与非邻近碎片相互作用相结合,有效地计算总QM能量.
- 方法参数调查为EE-GMFCC方法提供了最佳设置.
- 产生了一组高精度的蛋白质 - 配体相互作用能量数据集.
结论:
- 精细的EE-GMFCC[P-L]方法提供了一种高效和准确的方法来计算蛋白质 - 连接体相互作用能量.
- 生成的基准数据集是推进计算药物设计方法的宝贵资源.
- 这项工作有助于开发更近似但可靠的药物发现计算工具.
相关概念视频
02:49Calculating Standard Free Energy Changes
24.8K
The free energy change for a reaction that occurs under the standard conditions of 1 bar pressure and at 298 K is called the standard free energy change. Since free energy is a state function, its value depends only on the conditions of the initial and final states of the system. A convenient and common approach to the calculation of free energy changes for physical and chemical reactions is by use of widely available compilations of standard state thermodynamic data. One method involves the...
24.8K
02:40Ligand Binding Sites
15.0K
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...
15.0K
00:49Ligand Binding and Linkage
5.6K
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...
5.6K
02:31Habitat Fragmentation
21.3K
Habitat fragmentation describes the division of a more extensive, continuous habitat into smaller, discontinuous areas. Human activities such as land conversion, as well as slower geological processes leading to changes in the physical environment, are the two leading causes of habitat fragmentation. The fragmentation process typically follows the same steps: perforation, dissection, fragmentation, shrinkage, and attrition.
21.3K
02:51Metal-Ligand Bonds
24.2K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
24.2K
02:13Nuclear Binding Energy
14.7K
The difference between the calculated and experimentally measured masses is known as the mass defect of the atom. In the case of helium-4, the mass defect indicates a “loss” in mass of 4.0331 amu – 4.0026 amu = 0.0305 amu. The loss in mass accompanying the formation of an atom from protons, neutrons, and electrons is due to the conversion of that mass into energy that is evolved as the atom forms. The nuclear binding energy is the energy produced when the atoms’ nucleons are bound...
14.7K