Investigation of Long-Range Charge Transfer and Excited State Processes in Biochemical Systems

项目总结/摘要 在这个MIRA计划中，我们的目标是获得对复杂生物学的原子级见解。 系统如细菌膜蛋白和光敏蛋白， 强调其天然蛋白质和脂质环境。我们将测试这样的影响 生化环境中的两个不同的项目。 各种各样的有毒化学品，包括有毒的金属氧化物和氢氧化物， 环境，对人类生命构成迫在眉睫的威胁。人们可以利用独特的 希瓦氏菌等海洋微生物的呼吸机制， 生物修复和废水处理技术。分子建模和 计算将提供一个原子尺度的理解机制， 增加宏观实验观测量。在第一个项目中，我们将对 奥奈希瓦氏菌外膜细胞色素-孔蛋白复合体 环境，并获得分子的见解，电荷转移网络中采用的 它的呼吸 电子激发态过程在自然界和生物技术中无处不在。为 例如，蓝光敏感蛋白用于细胞的光遗传学控制， 流程.荧光蛋白的发射跨越整个可见光区， 通常用于体内成像。在这些应用中， 电子激发的分子在附近引起明显的构象变化， 蛋白质环境或远离其位置（变构）。因此，生物化学 环境将光子吸收位点处的信息中继到另一位点。最 构象变化发生的时间远远超过几纳秒， 现代多尺度量子力学/分子力学（QM/MM）无法实现 技术.因此，在第二个项目中，我们将建立一个工具来模拟激发态 的生物分子使用力场参数，然后验证这些参数使用 荧光蛋白的一些案例研究。此外，我们将使用这些参数来 破译蓝光敏感蛋白中的光诱导变构途径。

PROJECT SUMMARY/ABSTRACT In this MIRA program, we aim to gain atomic-level insights into complex biological systems such as bacterial membrane proteins and light-sensitive proteins with particular emphasis on their native protein and lipid environments. We will test the impact of such biochemical environments in two distinct projects. A wide variety of toxic chemicals, including toxic metal oxides and hydroxides, pollute our environment, posing an imminent threat to human life. One can leverage the unique respiration mechanism in marine microbes like Shewanella to revolutionize bioremediation and wastewater treatment technology. Molecular modeling and computations will provide an atomic-scale comprehension of the mechanism that will augment macroscale experimental observables. In the first project, we will model the outer membrane cytochrome-porin complex of Shewanella oneidensis in its native environment and obtain molecular insights into the charge-transfer network employed in its respiration. Electronically excited-state processes are ubiquitous in nature and biotechnology. For example, blue-light-sensitive proteins are used in the optogenetic control of cellular processes. Fluorescent proteins with emissions spanning the entire visible region are often utilized for in vivo imaging. In these applications, subtle structural changes in an electronically excited molecule induce pronounced conformational changes in the nearby protein environment or further from its location (allostery). Therefore, the biochemical environment relays the information at the photon-absorption site to another site. Most conformational changes occur well beyond a few nanoseconds, making them inaccessible to modern multi-scale quantum mechanics/molecular mechanics (QM/MM) techniques. Therefore, in the second project, we will build a tool to model excited states of biomolecules using force field parameters and then validate those parameters using a few case studies with fluorescent proteins. Furthermore, we will use those parameters to decipher photoinduced allosteric pathways in blue-light-sensitive proteins.