Department of Chemistry, Graduate School of Science, Kyoto University , Kyoto 606-8502, Japan.
J Phys Chem B. 2017 Apr 20;121(15):3842-3852. doi: 10.1021/acs.jpcb.6b13050. Epub 2017 Feb 27.
Rhodopsin is a G-protein coupled receptor functioning as a photoreceptor for vision through photoactivation of a covalently bound ligand of a retinal protonated Schiff base chromophore. Despite the availability of structural information on the inactivated and activated forms of the receptor, the transition processes initiated by the photoabsorption have not been well understood. Here we theoretically examined the photoactivation processes by means of molecular dynamics (MD) simulations and ab initio quantum mechanical/molecular mechanical (QM/MM) free energy geometry optimizations which enabled accurate geometry determination of the ligand molecule in ample statistical conformational samples of the protein. Structures of the intermediate states of the activation process, blue-shifted intermediate and Lumi, as well as the dark state first generated by MD simulations and then refined by the QM/MM free energy geometry optimizations were characterized by large displacement of the β-ionone ring of retinal along with change in the hydrogen bond of the protonated Schiff base. The ab initio calculations of vibrational and electronic spectroscopic properties of those states well reproduced the experimental observations and successfully identified the molecular origins underlying the spectroscopic features. The structural evolution in the formation of the intermediates provides a molecular insight into the efficient activation processes of the receptor.
视紫红质是一种 G 蛋白偶联受体，通过光激活视黄醛质子化席夫碱发色团的共价键配体，作为视觉的光感受器发挥作用。尽管已经获得了受体失活和激活形式的结构信息，但光吸收引发的转变过程仍未得到很好的理解。在这里，我们通过分子动力学（MD）模拟和从头算量子力学/分子力学（QM/MM）自由能几何优化来理论研究光激活过程，这使得在蛋白质的大量统计构象样本中能够准确确定配体分子的几何形状。通过 MD 模拟生成的激活过程的中间态、蓝移中间态和 Lumi 以及暗态的结构，以及通过 QM/MM 自由能几何优化进行的精细调整，其特征是视黄醛的 β-紫罗兰酮环发生大位移，同时质子化席夫碱的氢键发生变化。这些状态的振动和电子光谱性质的从头计算很好地再现了实验观察结果，并成功确定了光谱特征的分子起源。中间体形成过程中的结构演变提供了对受体高效激活过程的分子理解。
