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的从头计算电子结构计算的使用，例如，生化系统特别是，非线性光学性质的研究目前被限制在分子大小高达几百个原子，使他们不切实际的系统，如荧光蛋白。然而，为非线性光学成像显微镜设计新的明亮荧光蛋白作为遗传编码的生物标签需要对二次谐波产生（SHG）或双光子吸收（2 PA）等现象的理论理解。本项目旨在通过低成本的量子化学方法研究“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，主要考虑了最近发现的胆红素荧光蛋白，如UnaG及其衍生物。主要目标是提供关于如何改善其非线性光学性质的新见解，例如，通过微调蛋白质内部的发色团腔。这是一个重要的前景，因为较低强度的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，以获得设计原则，然后通过实验测试的合作者网络。在这种情况下，我们建立的简化的含时密度泛函理论（sTD-DFT）框架将被使用，并相应地扩展。更具体地说，目前还不可能用sTD-DFT计算精确的双光子跃迁。将进行方法开发，以纠正这一点，并提高2 PA横截面计算的准确性。现有的双电子积分近似将被取代的多极展开，包括所有的二阶项在计算效率的方式。我们将研究可能重新引入的交换相关内核的线性响应方程，可能需要准确的2 PA横截面。还将研究将轨道弛豫效应恢复为二次响应函数的问题。对于大型荧光蛋白，最初将使用扩展的紧密结合版本sTD-DFT-xTB。除了这个最小原子轨道基组xTB版本之外，还将开发用于大型系统的更一般的非自洽平均场电子结构理论（gTB，一般（基组）紧束缚），以提高准确性，特别是对于2 PA跃迁，其准确预测可能需要扩展基组。