Theoretical studies of nonlinear optical properties of fluorescent proteins by novel low-cost quantum chemistry methods

通过新型低成本量子化学方法对荧光蛋白非线性光学性质的理论研究

• 批准号: 450959503
• 负责人: Professor Dr. Stefan Grimme
• 金额: --
• 依托单位: Mulliken Center for Theoretical Chemistry
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/450959503?language=en
• 关键词: Theoretical; studies; nonlinear; optical; properties

The high computational cost limits the use of ab initio electronic structure calculations for large molecules, e.g., biochemical systems. Particularly, the investigation of nonlinear optical properties is currently restrained to molecules sizing up to a few hundred atoms, making them impractical for systems such as fluorescent proteins. Though, the design of new bright fluorescent proteins for nonlinear optical imaging microscopy as genetically-encoded bio-tags requires the theoretical understanding of phenomena such as second-harmonic generation (SHG) or two-photon absorption (2PA). This project aims at investigating nonlinear optical properties of “novel” (non-GFP) fluorescent proteins by low-cost quantum chemistry methods. In the application part of the proposal, mainly the recently discovered bilirubin fluorescent proteins such as UnaG and its derivatives are considered. The main goal is to provide new insights on how to improve their nonlinear optical properties, e.g., by fine-tuning of the chromophore cavity inside the protein. This is an important prospect because lower intensity laser light sources can reduce phototoxicity problems. A systematic theoretical procedure is proposed to obtain design principles, which are then tested experimentally by a network of collaborators. In this context, our well established simplified time-dependent density functional theory (sTD-DFT) framework will be used and accordingly extended. More specifically, it is not yet possible to compute accurate two-photon transitions with sTD-DFT. Method developments will be carried out to remedy this and to improve the accuracy for the calculation of 2PA cross-sections. The existing monopole approximation for the two-electron integrals will be replaced by a multipole expansion including all second-order terms in a computationally efficient manner. We will investigate the possible re-introduction of the exchange correlation kernel into the linear response equations that may be needed for accurate 2PA cross-sections. The re-instatement of orbital relaxation effects into the quadratic response function will be also investigated. For large fluorescent proteins, the extended Tight-Binding version sTD-DFT-xTB will be used initially. In addition to this minimal atomic orbital basis set xTB version, a more general, non-self-consistent mean-field electronic structure theory for large systems (gTB, general (basis set) Tight-Binding) will be developed for an improved accuracy in particular for 2PA transitions whose accurate prediction may require extended basis sets.

高计算成本限制了对大分子（例如生化系统）进行电子结构计算的使用。特别是，非线性光学性质的投资目前已恢复为尺寸高达几百个原子的分子，使其对于诸如荧光蛋白等系统不切实际。但是，作为一般编码的生物标记的非线性光学成像显微镜的新的明亮荧光蛋白的设计需要对现象（例如第二谐波生成（SHG）或两光子滥用（2PA））的理论理解。该项目旨在通过低成本量子化学方法研究“新型”（非GFP）荧光蛋白的非线性光学性质。在该提案的应用部分中，主要考虑了最近发现的胆红素荧光蛋白，例如Unag及其衍生物。主要目的是提供有关如何通过微粒体内蛋白质内部的发色团腔进行微调来提高其非线性光学特性的新见解。这是一个重要的前景，因为较低的强度激光光源可以减少光毒性问题。提出了一个系统的理论程序来获得设计原理，然后由合作者网络对其进行实验测试。在这种情况下，将使用并因此扩展了我们建立的简化时间相关的密度功能理论（STD-DFT）框架。更具体地说，尚无法使用STD-DFT计算准确的两光子过渡。将进行方法开发以记住这一点，并提高计算2PA横截面的准确性。两电子积分的现有单极近似将被多极扩展所取代，包括所有二阶项以计算有效的方式取代。我们将研究可能重新引入交换相关内核到线性响应方程中，这可能是准确的2PA横截面所需的。还将研究轨道放松效应到二次反应函数中的重新启动。对于大型荧光蛋白，最初将使用扩展的紧密结合版STD-DFT-XTB。除了这种最小的原子轨道基集XTB版本外，还将开发出更通用的，非自愿的大型系统（GTB，一般（基础）紧密结合）的平均值电子结构理论，以提高准确性，特别是对于2PA的过渡，其准确性预测可能需要扩展基础。