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

生化系统中长程电荷转移和激发态过程的研究

• 批准号: 10713085
• 负责人: Atanu Acharya
• 金额: $ 37.26万
• 依托单位: SYRACUSE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713085
• 关键词: Bacteria; Biochemical; Biochemical Process; Biochemistry; Bioremediations; Biotechnology; Breathing; Case Study; Cell physiology; Charge; Complex; Comprehension; Cytochromes; Environment; Human; Hydroxides; Investigation; Ions; Life; Light; Lipids; Location; Membrane; Membrane Proteins; Metals; Microbe; Modeling; Modernization; Molecular; Molecular Computations; Molecular Conformation; Nature; Pathway interactions; Photons; Poison; Pollution; Process; Proteins; Quantum Mechanics; Research; Respiration; Shewanella; Site; System; Techniques; Technology; Testing; VDAC1 gene; Vacuum; absorption; complex biological systems; in vivo imaging; insight; marine; metal oxide; molecular mechanics; molecular modeling; nanosecond; optogenetics; programs; tool; toxic metal

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.

项目摘要/摘要 在这个MIRA计划中，我们旨在获得对复杂生物学的原子水平的见解 诸如细菌膜蛋白和光敏蛋白等系统 强调其天然蛋白质和脂质环境。我们将测试这种影响 两个不同项目中的生化环境。 多种有毒化学物质，包括有毒金属氧化物和氢氧化物，污染了我们 环境，对人类生命构成迫在眉睫的威胁。一个人可以利用独特的 像Shewanella这样的海洋微生物中的呼吸机制以革新 生物修复和废水处理技术。分子建模和 计算将为原子级理解该机制的理解 增强宏观实验性可观察物。在第一个项目中，我们将建模 Shewanella Oneidensis的外膜细胞色素 - 菌群复合物 环境并获得对所采用的电荷转移网络的分子见解 它的呼吸。 电子激发状态的过程本质上是无处不在的。为了 例如，蓝光敏感蛋白用于细胞的光遗传控制 过程。横跨整个可见区域的排放量的荧光蛋白是 通常用于体内成像。在这些应用中，一个微妙的结构变化 电子激发的分子在附近引起明显的构象变化 蛋白质环境或离心的位置（变构）更远。因此，生化 环境将光子吸收位点的信息传递到另一个站点。最多 构象变化远远超出了几纳秒，使它们成为 无法访问现代多尺度量子力学/分子力学（QM/mm） 技术。因此，在第二个项目中，我们将建立一个工具来建模激发状态 使用力场参数的生物分子的生物分子，然后使用A 很少有荧光蛋白的案例研究。此外，我们将使用这些参数 解密光诱导的蓝光敏感蛋白中的变构途径。