QM/MM Studies of the Photochemistry of Biochromophores in Solution and in Protein Environments

吸收阳光的生物分子或蛋白质部分被称为生物发色团。这种具有光活性的生物分子可以被分类为光过滤器，它可以保护更敏感的生物结构（例如，晶状体中的犬尿氨酸保护视网膜免受紫外线损伤），或者作为生物分子机器，它利用阳光触发化学转化（例如，视网膜中的视紫红质）。通过研究生物发色团在其直接化学环境（无论是溶剂化壳还是蛋白质环境）中的光物理和光化学，可以深入了解自然界中基本的生理和生物光诱导分子过程。在此，我建议使用计算化学的方法研究两种生理和生物学相关的生物发色团在其自然化学环境中的光物理和光化学：嵌入在大量水中的皮肤紫外线过滤器尿尿酸和在蓝藻的光收集复合物中发现的光活性蛋白橙色类胡萝卜素蛋白（OCP），其特征是类胡萝卜素发色团。为了阐明分子的光化学反应性及其动力学行为，我设想使用静态方法来探索相关光化学过程的激发态势能面，以及通过执行非绝热分子动力学模拟的动态方法。这些研究将采用QM/MM方法进行，QM部分采用MS-CASPT2法测定尿酸，而基于gpu的SA-CASSCF在TeraChem中高效实现OCP的类胡萝卜素发色团。非绝热动力学模拟的从头算全多次生成方法应使用。我申请在斯坦福大学Todd J. Martínez教授的小组中进行这些研究。这些计划的成功实施将极大地推进对两种非常重要的生物分子的认识，并为这些分子的生物反应性的更大、更复杂的QM/MM研究铺平道路，这些分子的生物反应性是通过它们在自然环境中与各种反应伙伴的相互作用而获得的。

Sunlight-absorbing biomolecules or protein moieties are known as biochromophores. Such photoactive biomolecules can be classified either as light filters, which protect more sensitive biological structures (e.g. kynurenines in the ocular lens protecting the retina from UV damage), or as biomolecular machines, which use sunlight to trigger a chemical transformation (e.g. rhodopsin in the retina). Insight into fundamental physiological and biological photoinduced molecular processes in nature can be gained through the study of the photophysics and photochemistry of biochromophores embedded in their immediate chemical environment, either a solvation shell or a protein environment. Herein, I propose to study the photophysics and photochemistry of two physiologically and biologically relevant biochromophores in their natural chemical environment using methods of computational chemistry: the dermal UV filter urocanic acid embedded in bulk water and the photoactive protein Orange Carotenoid Protein (OCP) found in the light-harvesting complexes of cyanobacteria, which features a carotenoid chromophore. To elucidate the photochemical reactivity of the molecules as well as their dynamical behavior, I envision to use both a static approach for exploring excited-state potential-energy surfaces of relevant photochemical processes as well as a dynamical approach by performing nonadiabatic molecular-dynamics simulations. These studies shall be conducted with the QM/MM methodology employing for the QM part the MS-CASPT2 method for urocanic acid and a highly efficient GPU-based implementation of SA-CASSCF in TeraChem for the carotenoid chromophore of OCP. The ab initio full-multiple-spawning methodology shall be used for the nonadiabatic dynamics simulations. I apply to conduct these studies in the group of Prof. Todd J. Martínez at Stanford University. Successful implementation of these plans will significantly advance the knowledge on two highly important biomolecules and pave the way for even larger and more complex QM/MM studies of the biological reactivity of these molecules, which is given by their interaction with various reaction partners in their natural environment.