三氯叔丁醇影响缩宫素在溶液中分布行为的分子模拟

The MD simulation of the effect of chlorobutanol on the distribution of oxytocin in solution

目的:利用分子动力学(molecular dynamic,MD)模拟方法研究三氯叔丁醇对缩宫素在水溶液中分布行为的影响。方法:以Schr9dinger软件构建不同数量缩宫素和三氯叔丁醇与7 500个水分子的5个体系,以AMBERTOOL12设置体系力场参数,以Gromacs软件采用AMBER03力场进行10 ns的NVT模拟,记录模拟轨迹,计算均方位移(MSD)、扩散系数、氢键、相互作用残基等参数。结果:缩宫素在水中是一种逐步聚集的动态过程,500个三氯叔丁醇对10个缩宫素分散良好,增加三氯叔丁醇到1 000个分子可以导致缩宫素在三氯叔丁醇相中聚集。水中缩宫素参与聚集的氨基酸随机性较大,在三氯叔丁醇相中的聚集为首尾相互作用。三氯叔丁醇的加入可以降低缩宫素与水氢键相互作用。结论:缩宫素在水中有自聚的倾向,在适当浓度下三氯叔丁醇具有明显的分散作用。

Objective： Study the effects of chlorobutanol on the distribution of oxytocin in solution with molecular dynamic （MD） simulation method. Methods： 5 systems including chlorobutanol, oxytocin and 7 500 water molecules were constructed with Schrodinger software. Simulation paramters were established with AMBERTOOL12, and then transferred into Gromacs format. AMBER03 was used as force field in molecular dynamic （MD） simulations. The simulation time was 10 ns in NVT sytems. MSD, diffusion coefficient, hydrogen bond, and residue number within 0.35 nm were calculated. Results： Oxytocin molecules tended to gather gradually in water during MD simulation period. 10 oxytocin molecules were dispersed well after the addition of 500 chlorobutanol molecules, and could aggregate in 1 000 chlorobutanol molecules. In water solution, the residues related to oxytocin aggregation were random. While in solution with chlorobutanol, the interaction residues between oxytocin molecules were mainly head and tail residues. The addition of chlorobutanol can reduce the number of hydrogen bond between oxytocin and water. Conclusions： Oxytocin tends to aggregate in solution. The addition of chlorobutanol into solution can prevent oxytocin from aggregating.