通过热力学集成预测相分离蛋白的和度
Eduardo Pedraza1, Andres R Tejedor1,2, Alejandro Feito1
1Department of Physical Chemistry, Universidad Complutense de Madrid, Avenue Complutense s/n, Madrid 28040, Spain.
Journal of chemical theory and computation
|September 19, 2025
概括
我们开发了新的模拟方法,以准确测量蛋白质凝结物形成度. 这可以更好地比较计算模型和生物分子相位分离的实验数据.
科学领域:
- 生物物理和计算生物学
- 分子和细胞生物学分子和细胞生物学
背景情况:
- 生物分子凝结物通过相分离来调节细胞过程.
- 和度 (C_sat) 对于凝结物形成至关重要,但难以准确模拟.
- 目前的模拟方法缺乏用于精确C_sat测定的统计能力.
研究的目的:
- 开发可靠的模拟技术,用于准确的C_sat和相位图计算.
- 为了能够直接比较模拟结果和生物分子相位分离的实验数据.
- 验证和改进粗粒度模型来预测蛋白质凝结物的行为.
主要方法:
- 引入了两个独立的热力学集成 (TI) 方案.
- 结合TI与直接共存模拟使用Mpipi-Recharged模型.
- 将TI方法与机器学习预测器进行比较,用于C_sat估计.
主要成果:
- 准确估计各种蛋白质的C_sat,包括与疾病相关的和工程变异.
- 能够计算完整的相位图,揭示相位分离的分子机制.
- TI方法为验证生物分子模拟模型提供了物理基础的框架.
结论:
- 新的TI方案准确地确定生物分子凝聚物的C_sat和相位图.
- 这种方法弥合了计算模拟和实验观测之间的差距.
- 加强粗粒度模型的验证,以预测蛋白质相位行为.
相关概念视频
Phase Transitions: Melting and Freezing
14.6K
Heating a crystalline solid increases the average energy of its atoms, molecules, or ions, and the solid gets hotter. At some point, the added energy becomes large enough to partially overcome the forces holding the molecules or ions of the solid in their fixed positions, and the solid begins the process of transitioning to the liquid state or melting. At this point, the temperature of the solid stops rising, despite the continual input of heat, and it remains constant until all of the solid is...
14.6K
Phase Transitions: Sublimation and Deposition
19.7K
Some solids can transition directly into the gaseous state, bypassing the liquid state, via a process known as sublimation. At room temperature and standard pressure, a piece of dry ice (solid CO2) sublimes, appearing to gradually disappear without ever forming any liquid. Snow and ice sublimate at temperatures below the melting point of water, a slow process that may be accelerated by winds and the reduced atmospheric pressures at high altitudes. When solid iodine is warmed, the solid sublimes...
19.7K
Optimizing Chromatographic Separations
897
Optimizing chromatographic separations is crucial for obtaining clean separations in a minimum amount of time. Optimization is required for several factors, including kinetic effects related to band broadening, plate height, capacity factor, and separation factor.
Band broadening refers to spreading solute bands as they travel through the column. This broadening can impact resolution. Plate height (H) represents the length required for one theoretical plate. A lower plate height corresponds to...
Band broadening refers to spreading solute bands as they travel through the column. This broadening can impact resolution. Plate height (H) represents the length required for one theoretical plate. A lower plate height corresponds to...
897
Extraction: Partition and Distribution Coefficients
4.6K
The distribution law or Nernst's distribution law is the law that governs the distribution of a solute between two immiscible solvents. This law, also known as the partition law, states that if a solute is added to the mixture of two immiscible solvents at a constant temperature, the solute is distributed between the two solvents in such a way that the ratio of solute concentrations in the solvents remains constant at equilibrium.
For extracting a solute from an aqueous phase into an...
For extracting a solute from an aqueous phase into an...
4.6K
Enthalpy of Solution
30.0K
There are two criteria that favor, but do not guarantee, the spontaneous formation of a solution:
30.0K
Analyte Adsorption and Distribution
2.5K
In certain chromatographic separations, solutes transfer between the mobile phase and the stationary phase via sorption, which typically refers to the process of adsorption. For many chromatographic systems, the sorption process often depends on the polarity of the compounds—an expression of the overall dipole moment within the molecule. During the separation process, there is competition between the solute and solvent for adsorption to the stationary phase. Highly polar compounds and...
2.5K


