Center for Biophysics and Quantitative Biology, University of Illinois, Urbana, IL, U.S.A.
Department of Plant Biology, University of Illinois, Urbana, IL, U.S.A.
Biochem J. 2018 Mar 9;475(5):905-921. doi: 10.1042/BCJ20170299.
Eukaryotic protein kinases (PKs) are a large family of proteins critical for cellular response to external signals, acting as molecular switches. PKs propagate biochemical signals by catalyzing phosphorylation of other proteins, including other PKs, which can undergo conformational changes upon phosphorylation and catalyze further phosphorylations. Although PKs have been studied thoroughly across the domains of life, the structures of these proteins are sparsely understood in numerous groups of organisms, including plants. In addition to efforts towards determining crystal structures of PKs, research on human PKs has incorporated molecular dynamics (MD) simulations to study the conformational dynamics underlying the switching of PK function. This approach of experimental structural biology coupled with computational biophysics has led to improved understanding of how PKs become catalytically active and why mutations cause pathological PK behavior, at spatial and temporal resolutions inaccessible to current experimental methods alone. In this review, we argue for the value of applying MD simulation to plant PKs. We review the basics of MD simulation methodology, the successes achieved through MD simulation in animal PKs, and current work on plant PKs using MD simulation. We conclude with a discussion of the future of MD simulations and plant PKs, arguing for the importance of molecular simulation in the future of plant PK research.
真核蛋白激酶 (PKs) 是一类对细胞对外界信号的反应至关重要的蛋白质大家族，充当着分子开关的作用。PKs 通过催化其他蛋白质的磷酸化来传递生化信号，包括其他 PKs，这些蛋白质在磷酸化后会发生构象变化，并进一步催化磷酸化。尽管 PKs 在生命领域的各个方面都得到了深入研究，但这些蛋白质的结构在包括植物在内的许多生物群体中仍然知之甚少。除了努力确定 PK 的晶体结构外，对人类 PK 的研究还结合了分子动力学 (MD) 模拟，以研究 PK 功能转换背后的构象动力学。这种实验结构生物学与计算生物物理学相结合的方法，提高了我们对 PK 如何变得具有催化活性以及为什么突变会导致病理性 PK 行为的理解，而这些都是当前单独使用实验方法无法达到的空间和时间分辨率。在这篇综述中，我们主张将 MD 模拟应用于植物 PK 的价值。我们回顾了 MD 模拟方法的基础知识、MD 模拟在动物 PK 中取得的成功，以及当前使用 MD 模拟研究植物 PK 的工作。最后，我们讨论了 MD 模拟和植物 PK 的未来，认为分子模拟在植物 PK 研究的未来中非常重要。
