Simulation of the light-induced conformational dynamics in the AppA BLUF domain

在通过其黄素发色团（黄素腺嘌呤二核苷酸，FAD）吸收光之后，Rhb中转录抗阻遏蛋白AppA的蓝光敏感BLUF（使用黄素的蓝光传感）结构域。球状体在亚纳秒时间尺度上从暗适应（DA）状态构象转换到构象不同的光适应（LA）状态。本研究的目的是在分子力学的框架内，通过分子动力学模拟来描述这种光诱导构象弛豫动力学。为了检查模拟预测的蛋白质构象（da，中间体，la）的有效性，我们将使用混合方法计算原位FAD发色团的相关振动光谱，并将结果与相应的实验数据进行比较。混合方法结合联合收割机的FAD发色团的密度泛函理论的框架中的分子力学模型的蛋白质和溶剂环境的量子力学描述。模拟的目的是有助于澄清的机制，通过该机制，AppA BLUF将光的吸收转化为生物化学可检测的信息和光合作用基因的调节。该项目要求并旨在与研究小组内外的其他团体密切合作。

After light absorption by its flavin chromophore (flavin adenine dinucleotide, FAD), the blue light sensitive BLUF (Blue Light sensing Using Flavin) domain of the transcriptional antirepressor protein AppA in Rhb. sphaeroides is conformationally switched on a subnanosecond time scale from a dark-adapted (da) state to a conformationally different light-adapted (la) state. It is the aim of this project to describe this light-induced conformational relaxation dynamics within the framework of molecular mechanics by molecular dynamics simulations. To check the validity of the protein conformations (da, intermediates, la) predicted by the simulations we will compute the associated vibrational spectra for the FAD chromophore in situ using hybrid methods and will compare the results with corresponding experimental data. The hybrid methods combine a quantum mechanical description of the FAD chromophore in the framework of density functional theory with a molecular mechanics model of the protein and solvent environment. The simulations aim at contributing to the clarification of the mechanisms, by which AppA BLUF converts the absorption of light into biochemically detectable information and the regulation of photosynthesis genes. The project requires and aims at close cooperations with other groups within and beyond the Forschergruppe.