Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Göteborg, Sweden.
J Chem Inf Model. 2013 Jul 22;53(7):1736-46. doi: 10.1021/ci4001822. Epub 2013 Jun 24.
The dimeric UVR8 protein is an ultraviolet-B radiation (280-315 nm) photoreceptor responsible for the first step in UV-B regulation of gene expression in plants. Its action comprises the actual absorption of the UV quanta by a tryptophan array at the protein-protein interface, followed by monomerization and subsequent aggregation with downstream signaling components. A crystal structure of the Arabidopsis thaliana tryptophan-rich wild type UVR8 protein dimer was recently published, showing the presence of several salt bridges involving arginines R146, R286, R338, and R354. In this work, molecular dynamics simulations in conjunction with umbrella sampling were used to calculate the binding free energy for the wild type UVR8 dimer and three of its mutants (R286A, R338A, and R286A/R338A), in order to verify whether the key mutants are able to disrupt the dimeric structure as indicated experimentally.
二聚体 UVR8 蛋白是一种紫外线-B 辐射（280-315nm）光受体，负责植物中 UV-B 调控基因表达的第一步。其作用包括通过蛋白质-蛋白质界面上的色氨酸序列实际吸收 UV 量子，然后单体化，随后与下游信号传导成分聚集。最近发表了拟南芥富色氨酸野生型 UVR8 蛋白二聚体的晶体结构，显示存在几个涉及精氨酸 R146、R286、R338 和 R354 的盐桥。在这项工作中，使用分子动力学模拟结合伞状采样来计算野生型 UVR8 二聚体及其三个突变体（R286A、R338A 和 R286A/R338A）的结合自由能，以验证关键突变体是否能够像实验所示那样破坏二聚体结构。
