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.

高计算成本限制了从头算电子结构计算在大分子（例如生化系统）中的使用，特别是，非线性光学性质的研究目前仅限于大小高达数百个原子的分子，这使得它们对于诸如生化系统之类的系统不切实际。然而，设计用于非线性光学成像显微镜的新型明亮荧光蛋白作为基因编码生物标签需要对二次谐波产生（SHG）或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特性，在该提案的应用部分，主要是最近发现的胆红素荧光蛋白。主要目标是提供关于如何改善其非线性光学特性的新见解，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，因为激光强度较低。提出了一个系统的理论程序来获得设计原理，然后由合作者网络进行实验测试，在此背景下，我们完善的简化的时间相关密度泛函理论（sTD-DFT）框架将被提出。更具体地说，尚无法使用 sTD-DFT 计算精确的双光子跃迁，以弥补这一问题并提高现有 2PA 截面的计算精度。单极子双电子积分的近似将以计算有效的方式被包括所有二阶项的多极展开式所取代，我们将研究可能需要将交换相关核重新引入线性响应方程中，以实现精确。还将研究将轨道弛豫效应重新恢复到二次响应函数中。对于大型荧光蛋白，还将研究扩展的紧密结合版本 sTD-DFT-xTB。除了最初使用的最小原子轨道基组 xTB 版本之外，还将开发一个更通用的、非自洽的大型系统平均场电子结构理论（gTB，通用（基组）紧束缚）。提高了准确性，特别是 2PA 转换，其准确预测可能需要扩展的基础集。