结合光谱法和计算模拟分析CYP3A4酶与己烯雌酚的作用机制

Interaction between Diethylstilbestrol and CYP3A4 based on multi-spectrum methods and computational simulations

本文结合分子对接、动力学模拟和光谱法,研究了己烯雌酚(Diethylstilbestrol,DES)与CYP3A4酶在模拟生理环境下(pH7.4)的相互作用机制.利用分子对接和动力学模拟方法从理论上模拟CYP3A4与DES相互作用后的构象变化情况.通过光谱法从实验角度进行验证,荧光光谱得出DES对CYP3A4的猝灭机制属于静态猝灭,红外和紫外光谱结果表明, DES与CYP3A4结合后,改变了CYP3A4的内部环境和构象.理论模拟和实验结果相互印证,为探究DES和CYP3A4的相互作用提供了重要信息和参考依据.

The interaction mechanism between Diethylstilbestrol(DES) and CYP3A4 enzyme in simulated physiological environment(pH=7.4) was studied by molecular docking, kinetic simulation and spectrometric method. The molecular docking and dynamics simulation were used to simulate the conformation changes of CYP3A4 and DES in theory. Then, it was experimental verified by spectral methods. The fluorescence spectra showed that the quenching mechanism of CYP3A4 by DES was static quenching. The results of IR and UV spectra showed that the internal environment and conformation of CYP3A4 were changed after DES interacted with CYP3A4. The theoretical simulation and experimental results were consistent with each other, which provides important information and reference for exploring the interaction between DES and CYP3A4.