在全原子和粗粒度模拟中探索自由能量景观,以分离蛋白质成膜域
Seulki Kwon1, Ayan Majumder1, John E Straub1
1Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
Journal of chemical theory and computation
|November 1, 2024
概括
准确计算膜域之间的蛋白质分区需要进行全原子模拟. 这项研究引入了一种有效的自由能量计算方法,这对于理解膜生物物理学和蛋白质行为至关重要.
科学领域:
- 膜生物物理学 膜生物物理学
- 计算生物物理学的计算生物物理.
- 分子建模分子建模
背景情况:
- 细胞膜的脂质环境显著影响了整体膜蛋白质的结构和功能.
- 了解不同膜域之间的蛋白质分区是膜生物物理学的关键.
- 分子动力学 (MD) 模拟对于量化蛋白质分割的自由能量场景至关重要.
研究的目的:
- 开发一种高效的模拟方法来计算跨膜蛋白分离的自由能量.
- 使用全原子 (AA) 模型,比较液体无序 (Ld) 和液体有序 (Lo) 域之间的自由能量分区.
- 研究膜域之间蛋白质翻译背后的热力学驱动力.
主要方法:
- 使用全原子 (AA) 分子动力学模拟用于相分离的脂质双层.
- 计算了平均力 (PMF) 的潜力,以确定平衡分区系数.
- 使用能量分解分析来识别热力学差异.
- 从AA模拟与粗粒度 (CG) 模型进行比较的结果.
主要成果:
- 开发了一种高效的AA模拟方法来计算蛋白质分区的自由能量.
- 在AA和CG模型之间的计算分区系数中证明了显著的差异.
- 确定了影响蛋白质分裂的特定热力学贡献.
结论:
- 全原子模拟对于准确估计蛋白质域转换过程中的自由能量变化至关重要.
- 拟议的方法提供了一种定量方法来研究蛋白质-脂质相互作用.
- 这些发现强调了高分辨率模型对于准确的生物物理预测的必要性.
相关概念视频
Protein Diffusion in the Membrane
4.3K
Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
4.3K
Mechanisms of Membrane Domain Formation
3.0K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.0K
Membrane Domains
5.3K
The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
5.3K
Membrane Fluidity
11.0K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
11.0K
Conservation of Protein Domains Over Different Proteins
10.8K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K
Fluid Mosaic Model
11.5K
Scientists identified the plasma membrane in the 1890s and its principal chemical components (lipids and proteins) by 1915. The model for plasma membrane structure, proposed in 1935 by Hugh Davson and James Danielli, was the first model to be widely accepted in the scientific community. The model was based on the plasma membrane's "railroad track" appearance in early electron micrographs. Davson and Danielli theorized that the plasma membrane's structure resembled a sandwich...
11.5K


