Automated QM/MM Screening of Rhodopsin Variants with Enhanced Fluorescence.
Automated QM/MM Screening of Rhodopsin Variants with Enhanced Fluorescence.
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DOI：
10.1021/acs.jctc.2c00928
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发表时间：
2022-12
影响因子：
5.5
通讯作者：
Laura Pedraza-González;L. Barneschi;M. Marszałek;Daniele Padula;L. De Vico;M. Olivucci
中科院分区：
文献类型：
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作者：
Laura Pedraza-González;L. Barneschi;M. Marszałek;Daniele Padula;L. De Vico;M. Olivucci
我们提出了一个计算协议的快速和自动筛选的激发态混合量子力学/分子力学（QM/MM）模型的视紫红质被用作荧光探针的基础上的自动视紫红质建模协议（a-ARM）。这种“a-ARM荧光筛选协议”是通过一个通用的基于Python的驱动程序，PyARM，这也是在这里提出的。该协议的实施和性能的基准使用不同的视紫红质变体的吸收，更相关的是，发射光谱已经实验测量。我们表明，尽管重要的限制，使不安全的使用它作为一个黑盒工具，该协议再现了观察到的荧光趋势，它是能够选择新的潜在荧光视紫红质。我们还表明，该协议可用于在机制的调查，以辨别荧光增强效应与近简并的S1/S2状态，或者，通过耦合的S 0/S1波函数产生的障碍。
We present a computational protocol for the fast and automated screening of excited-state hybrid quantum mechanics/molecular mechanics (QM/MM) models of rhodopsins to be used as fluorescent probes based on the automatic rhodopsin modeling protocol (a-ARM). Such "a-ARM fluorescence screening protocol" is implemented through a general Python-based driver, PyARM, that is also proposed here. The implementation and performance of the protocol are benchmarked using different sets of rhodopsin variants whose absorption and, more relevantly, emission spectra have been experimentally measured. We show that, despite important limitations that make unsafe to use it as a black-box tool, the protocol reproduces the observed trends in fluorescence and it is capable of selecting novel potentially fluorescent rhodopsins. We also show that the protocol can be used in mechanistic investigations to discern fluorescence enhancement effects associated with a near degeneracy of the S1/S2 states or, alternatively, with a barrier generated via coupling of the S0/S1 wave functions.