中文摘要：

通过生物信息学分析、量化计算优化、CAVER和MDpocket预测、随机加速分子动力学及伞状抽样动力学模拟等方法,对喹啉加氧酶（HOD）中的氧气扩散途径进行了计算预测.结果表明,氧气在HOD中的反应位点包埋在蛋白内部,而HOD中有数条可能的通道供氧气进出,其中长度最短的通道具有最高的优先度,不仅在随机加速动力学模拟中具有最高的氧气逸出概率,而且伞状抽样方法计算得到的自由能也最低.此通道的内端位于底物Re面的氧气结合位点,较好地解释了HOD的相关实验数据.

英文摘要：

Oxygen diffusion pathways of quinoline oxygenase（ HOD） were investigated by bioinformatics analysis,quantum chemical optimization,CAVER and MD pocket prediction,random accelerated molecular dynamics simulations and umbrella sampling. The results show that the pre-reaction site of oxygen does locate inside the active pocket,and there exists several possible oxygen tunnels in HOD,in which the one with shortest length has the highest priority. Random accelerated molecular dynamics proved that oxygen has the highest probability to exit from this tunnel,and umbrella sampling further verified its free energy for oxygen passing by is the lowest. The tunnel ended at the binding site of oxygen located on the Re-face of the substrate,which is consistent with previous studies. These results better illuminate the kinetics and the stereo-selectivity of the catalytic reaction in HOD,and also provide theoretical guidance to further experimentally improve the efficiency of oxygen usage by enzyme.