Rational designing of 8-hydroxyquinolin-imidazolinone-based fluorescent protein mutants with dramatically red shifted emission: A computational study,Journal of Computational Chemistry

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Rational designing of 8-hydroxyquinolin-imidazolinone-based fluorescent protein mutants with dramatically red shifted emission: A computational study
Journal of Computational Chemistry ( IF 3.4 ) Pub Date : 2018-10-14 , DOI: 10.1002/jcc.25552
Xian Chen _{1,

2} , Jian Song ₃ , Zhe-Ning Chen ₂ , Tan Jin ₂ , Fengqin Long ₂ , Hua Xie ₂ , Yisong Zheng ₁ , Wei Zhuang ₂ , Lu Zhang ₂

Affiliation

Engineering fluorescent proteins to be the customized in vivo labels for monitoring cellular dynamic events is critical in biochemical and biomedical studies. The design and development of novel red fluorescent proteins is one of the most important fronts in this field due to their potential of imaging the entire organism. A recent fluorescent protein mutant eqFP650‐67‐HqAla with the 8‐hydroxyquinolin‐imidazolinone (HQI) chromophore has the plausible bathochromic shift of ~30 nm in its emission spectrum wavelength comparing to the parent fluorescent protein eqFP650. However, molecular mechanism of this significant shift remains somewhat obscure. In this study, we carefully benchmarked our computational methods and performed extensive calculations to investigate various structural components’ effect on the chromophore's emission energy and decipher the molecular origin of the spectral shift. The influences of conjugation size, substituent group, substituent site as well as the number of substituents have been examined by elaborately designed chromophore derivatives. Accordingly, we proposed several chromophore mutants with dramatic bathochromic shift of up to ~60 nm in their emission spectra. We further evaluated their structural stability in the protein using molecular dynamics simulations. Present theoretical study connects the structural feature of chromophore derivatives in red fluorescent proteins with their splendid performances in shifting the emission frequency and offer the molecular insight. The computational protocol and successive examination procedure to extract the structural effect utilized herein can also be widely applied to other fluorescent proteins in general. © 2018 Wiley Periodicals, Inc.

中文翻译：

具有显着红移发射的基于 8-羟基喹啉-咪唑啉酮的荧光蛋白突变体的合理设计：计算研究

将荧光蛋白工程化为监测细胞动态事件的定制体内标记在生化和生物医学研究中至关重要。新型红色荧光蛋白的设计和开发是该领域最重要的前沿之一，因为它们具有对整个生物体进行成像的潜力。与亲本荧光蛋白 eqFP650 相比，最近具有 8-羟基喹啉-咪唑啉酮 (HQI) 发色团的荧光蛋白突变体 eqFP650-67-HqAla 在其发射光谱波长中具有大约 30 nm 的红移。然而，这种重大转变的分子机制仍然有些模糊。在这项研究中，我们仔细地对我们的计算方法进行了基准测试，并进行了广泛的计算，以研究各种结构成分对发色团发射能量的影响，并破译光谱位移的分子起源。通过精心设计的发色团衍生物，研究了共轭尺寸、取代基、取代位点以及取代基数量的影响。因此，我们提出了几种发色团突变体，其发射光谱具有高达约 60 nm 的剧烈红移。我们使用分子动力学模拟进一步评估了它们在蛋白质中的结构稳定性。目前的理论研究将红色荧光蛋白中发色团衍生物的结构特征与其在改变发射频率方面的出色性能联系起来，并提供分子洞察。此处使用的提取结构效应的计算方案和连续检查程序通常也可以广泛应用于其他荧光蛋白。 © 2018 Wiley 期刊公司。

更新日期：2018-10-14

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