细菌生物发光机理的计算模拟

There are many living beings can emit visible light in the nature. One hundred and tens of bacteria can emit green-blue light. The biological insgiht of the bacterial bioluminescence has not been totally understood. The mechanism of the bacterial bioluminescence has not been explained in a clear way. Compared the other bioluminescence phenomena, the experimental studies on the bacterial bioluminescence are rather less and there is no any level of quantum chemical study. One thing for sure is that the bioluminescence mechanism of bacterium and animal is totally different. The bacterial bioluminescence is sensitive to the concentration of pollutent in environment, which can stably,sensitively and rapidly reflects the change of the pollutant concentration and has become the hot topic of the research and development on sensor. This project will start from the luciferine of the luminous bacteria to build all kinds of computational models from small to large untill including the whole protein environment, then theoretically simulate the bioluminescence process systematically. The theoretical study will employ methods of quantum chemistry, the combination of quantum mechanics and molecular mechanics and molecular dynamics to consider the effect of protein environment to the excited state of light emitter, the possible charge-transfer mechanism, the spectra and energetics of the bioluminescence process, and so on. The purpose of this project is to support the application of bacterial bioluminescence with theoretical evidences by understanding the nature, mechanism and chemical origin of bacterial bioluminescence at the molecualer level.

自然界中能够发可见光的生物很多，有一百几十种细菌可以发蓝到绿色的光。发光细菌的生物学意义还不清楚。关于其发光机理目前只是大概猜测，实验研究很少，还没有任何理论研究。可以肯定的是其发光机理与动物发光完全不同。细菌发光现象能够稳定、灵敏、快速地反映环境中污染物的浓度变化，已成为国内外传感器研究和发展的热点。本项目将从发光细菌的荧光素分子入手，建立从小到大直到包含整体蛋白环境的各种计算模型来循序渐进地模拟其发光过程。项目将使用量子化学、量子力学和分子力学相结合以及分子动力学的计算手段来考虑蛋白环境对发光体激发态的影响，可能的电子转移机理，以及发光过程的谱学和能量学等问题，以期在分子水平搞清细菌发光的本质、机理和化学起源，为其生物发光的实际应用提供理论依据和指导。

哈维氏弧菌的发光已经得到实际应用，但是其发光机理只有粗略的猜测。结合有限的实验信息，本项目首次对哈维氏弧菌的发光过程和机理进行了理论计算和多尺度模拟。清晰描述了从荧光素分子在荧光素酶的催化下加氧生成过氧键中间体以及过氧键热解离发出可见光的全过程。回答了上世纪七十年代 Hastings提出的两个科学问题：哈维氏弧菌的发光体是什么?为什么黄素单核苷酸分子(FMN)在荧光素酶中有应该猝灭现象？从理论计算的结果，我们指认了4a-羟基-5-氢取代的FMN（HFOH）是哈维氏弧菌生物发光的发光体。从荧光素酶的110号酪氨酸到FMN的单电子转移导致了FMN的荧光猝灭。这项研究在分子和电子态水平搞清了细菌发光的本质、机理和化学起源，必将为其生物发光的实际应用提供理论依据和指导。