Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.
Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.
J Phys Chem B. 2023 Nov 23;127(46):9863-9872. doi: 10.1021/acs.jpcb.3c05166. Epub 2023 Oct 4.
The cell is a crowded space where large biomolecules and metabolites are in continuous motion. Great strides have been made in studies of protein dynamics, folding, and protein-protein interactions, and much new data are emerging of how they differ in the cell. In this Perspective, we highlight the current progress in atomistic modeling of in-cell environments, both bacteria and mammals, with emphasis on classical all-atom molecular dynamics simulations. These simulations have been recently used to capture and characterize functional and non-functional protein-protein interactions, protein folding dynamics of small proteins with varied topologies, and dynamics of metabolites. We further discuss the challenges and efforts for updating modern force fields critical to the progress of cellular environment simulations. We also briefly summarize developments in relevant state-of-the-art experimental techniques. As computational and experimental methodologies continue to progress and produce more directly comparable data, we are poised to capture the complex atomistic picture of the cell.
细胞是一个拥挤的空间，其中大分子生物和代谢物处于持续运动中。在蛋白质动力学、折叠和蛋白质-蛋白质相互作用的研究方面已经取得了重大进展，大量新的数据表明它们在细胞中的差异。在这篇观点文章中，我们重点介绍了目前在细菌和哺乳动物的细胞内环境的原子建模方面的进展，重点是经典的全原子分子动力学模拟。这些模拟最近被用于捕获和描述功能和非功能的蛋白质-蛋白质相互作用、具有不同拓扑结构的小蛋白质的折叠动力学以及代谢物的动力学。我们进一步讨论了更新对细胞环境模拟至关重要的现代力场的挑战和努力。我们还简要总结了相关最先进的实验技术的发展。随着计算和实验方法的不断进步并产生更直接可比的数据，我们有望捕捉到细胞的复杂原子图像。
