含APP C99的三元脂质混合物相分离动力学和机理:原子与粗粒度MD模拟。

IF 5.7 1区 化学 Q2 CHEMISTRY, PHYSICAL
Journal of Chemical Theory and Computation Pub Date : 2025-05-27 Epub Date: 2025-05-15 DOI:10.1021/acs.jctc.5c00016
George A Pantelopulos, Sangram Prusty, Asanga Bandara, John E Straub
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引用次数: 0

摘要

由饱和脂质和不饱和脂质与胆固醇混合物组成的脂质双层的相分离是膜生物物理学和细胞生物学的一个重要课题。脂质结构域的形成,包括富含不饱和脂质的液体无序结构域和富含饱和脂质和胆固醇的液体有序结构域,被认为对许多膜蛋白的功能至关重要。实验,理论和模拟已经被用来发展的热力学驱动力的基本理解相分离在三元和四元脂质混合物。然而,在跨膜蛋白存在的情况下,脂相分离早期事件的动力学研究仍然相对不足。利用大规模的全原子和粗粒度模拟,我们探索了在跨膜蛋白存在下饱和脂、不饱和脂和胆固醇三元脂混合物的动力学和相分离。Cahn-Hilliard理论中使用的有序参数提供了对脂相分离动力学和机理的深入了解。我们在相分离过程中观察到三个不同的时间制度:一个较短的指数时间阶段,其次是幂律阶段,然后是较长的平台阶段。比较全原子模型和粗粒度模型之间的脂质、蛋白质和脂质-蛋白质动力学,确定了相分离动力学的定量和定性差异和相似性。此外,AA和CG模拟的动力学时间尺度得出了相似的相分离动力学机制。本研究的发现阐明了膜生物物理学的基本方面,并有助于持续努力定义脂筏在细胞膜结构和功能中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kinetics and Mechanism of Phase Separation in Ternary Lipid Mixtures Containing APP C99: Atomistic vs Coarse-Grained MD Simulations.

The phase separation of lipid bilayers, composed of mixtures of saturated and unsaturated lipids and cholesterol, is a topic of fundamental importance in membrane biophysics and cell biology. The formation of lipid domains, including liquid-disordered domains enriched in unsaturated lipids and liquid-ordered domains enriched in saturated lipids and cholesterol, is believed to be essential to the function of many membrane proteins. Experiment, theory, and simulation have been used to develop a general understanding of the thermodynamic driving forces underlying phase separation in ternary and quaternary lipid mixtures. However, the kinetics of early events in lipid phase separation in the presence of transmembrane proteins remain relatively understudied. Using large-scale all-atom and coarse-grained simulations, we explore the kinetics and phase separation of ternary lipid mixtures of saturated lipid, unsaturated lipid, and cholesterol in the presence of transmembrane proteins. Order parameters employed in the Cahn-Hilliard theory provide insight into the kinetics and mechanism of lipid phase separation. We observe three distinct time regimes in the phase separation process: a shorter exponential time phase, followed by a power-law phase, and then a longer plateau phase. Comparison of lipid, protein, and lipid-protein dynamics between all-atom and coarse-grained models identifies both quantitative and qualitative differences and similarities in the phase separation kinetics. Moreover, timescaling of the dynamics of the AA and CG simulations yields a similar kinetic mechanism of phase separation. The findings of this study elucidate fundamental aspects of membrane biophysics and contribute to ongoing efforts to define the role of lipid rafts in the structure and function of the cellular membrane.

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来源期刊
Journal of Chemical Theory and Computation
Journal of Chemical Theory and Computation 化学-物理:原子、分子和化学物理
CiteScore
9.90
自引率
16.40%
发文量
568
审稿时长
1 months
期刊介绍: The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.
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