PDF(Pubmed)
Abstract：
Cryptochromes are essential flavoproteins for circadian rhythms and avian magnetoreception. Flavin adenine dinucleotide (FAD), a chromophore within cryptochromes, absorbs blue light, initiating electron transfer processes that lead to a biological signaling cascade. A key step in this cascade is the formation of the FAD semiquinone radical (FADH•), characterized through a specific red-light absorption. The absorption spectra of FADH• in cryptochromes are, however, significantly different from those recorded for the cofactor in solution, primarily due to protein-induced shifts in the absorption peaks. This study employs a multiscale approach, combining molecular dynamics (MD) simulations with quantum mechanical/molecular mechanical (QM/MM) methodologies, to investigate the influence of protein dynamics on embedded FADH• absorption. We emphasize the role of the protein\'s polarizable environment in the shaping of the absorption spectrum, crucial for accurate spectral predictions in cryptochromes. Our findings provide valuable insights into the absorption process, advancing our understanding of cryptochrome functioning.
摘要：
隐色素是昼夜节律和鸟类磁接收的必需黄素蛋白。黄素腺嘌呤二核苷酸（FAD），隐色素中的发色团，吸收蓝光，启动导致生物信号级联的电子转移过程。该级联的关键步骤是FAD半醌自由基（FADH•）的形成，通过特定的红光吸收。隐色染料中FADH·的吸收光谱为，然而,与溶液中辅因子的记录显着不同，主要是由于蛋白质诱导的吸收峰的偏移。本研究采用多尺度方法，将分子动力学（MD）模拟与量子力学/分子力学（QM/MM）方法相结合，研究蛋白质动力学对包埋FADH·吸收的影响。我们强调蛋白质的可极化环境在吸收光谱形成中的作用，对于隐色光谱的准确预测至关重要。我们的发现为吸收过程提供了宝贵的见解，推进我们对隐铬功能的理解。
