Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. Electronic address: https://twitter.com/huhlim.
Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Computational Biophysics Research Team, RIKEN Center for Computational Science, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Curr Opin Struct Biol. 2022 Apr;73:102340. doi: 10.1016/j.sbi.2022.102340. Epub 2022 Feb 23.
Proteins encounter frequent molecular interactions in biological environments. Computer simulations have become an increasingly important tool in providing mechanistic insights into how such interactions in vivo relate to their biological function. The review here focuses on simulations describing protein assembly and molecular crowding effects as two important aspects that are distinguished mainly by how specific and long-lived protein contacts are. On the topic of crowding, recent simulations have provided new insights into how crowding affects protein folding and stability, modulates enzyme activity, and affects diffusive properties. Recent studies of assembly processes focus on assembly pathways, especially for virus capsids, amyloid aggregation pathways, and the role of multivalent interactions leading to phase separation. Also, discussed are technical challenges in achieving increasingly realistic simulations of interactions in cellular environments.
蛋白质在生物环境中经常会遇到分子相互作用。计算机模拟已成为提供机制见解的重要工具，这些见解涉及体内这些相互作用与其生物功能的关系。本文综述主要集中在描述蛋白质组装和分子拥挤效应的模拟上，这两个方面的主要区别在于蛋白质接触的特异性和持久性。关于拥挤效应，最近的模拟提供了新的见解，说明拥挤如何影响蛋白质折叠和稳定性、调节酶活性以及影响扩散性质。最近对组装过程的研究主要集中在组装途径上，特别是病毒衣壳、淀粉样蛋白聚集途径以及多价相互作用导致相分离的作用。还讨论了在实现越来越真实的细胞环境中相互作用模拟方面的技术挑战。
