NaCl浓度改变对人类神经元钙传感蛋白结构的影响:来自分子动力学模拟证据  

Variations of sodium chloride concentration affect conformational dynamics of human neuronal calcium sensor-1 protein: a molecular dynamics simulation study

作　　者：朱玉珍[1] 李云翔 蔡皓[1] 张庆文[2] Zhu Yu-zhen1, Li Yun-xiang1, Cai Hao1, Zhang Qing-wen2(1.Physical Education College, Shanghai Normal University, Shanghai 200234, China; 2.Shanghai University of Sport, Shanghai 200438, Chin)

机构地区：[1]上海师范大学体育学院,上海市200234 [2]上海体育学院,上海市200438

出　　处：《中国组织工程研究》2018年第16期2549-2557,共9页Chinese Journal of Tissue Engineering Research

基　　金：上海高校青年教师培养资助项目(A-9103-17-041331);上海体育学院研究生教育创新科研项目(yjscx2015003)~~

摘　　要：背景:人类神经元钙传感蛋白是一个含有高电荷的蛋白,对溶液温度极其敏感,但溶液中离子浓度的变化是否能够改变蛋白结构,进而影响其正常功能的发挥,尚未发现相关研究。目的:探讨溶液中NaCl浓度的微小改变对人类神经元钙传感蛋白结构动力学影响的分子机制。方法:采用全原子计算机动力学模拟的方法,将蛋白质数据库中ID为2LCP的人类神经元钙传感蛋白前两个能量最低的结构作为初始结构,能量最小化后,将蛋白置于NaCl浓度分别为0.1,0.3和1 mol/L的水溶液中,以高速摄像速度(ps,10-12s)记录蛋白在模拟体系中的运行和变化情况。结果与结论:溶液中NaCl浓度升高,(1)人类神经元钙传感蛋白柔性增加,整体结构和局部的疏水口袋体积增大;(2)蛋白C端尾部L3蜷缩,首尾氨基酸D176和V190之间的次联系路径数量明显减少,导致两者之间的联系减弱;(3)蛋白N段和C段氨基酸之间的联系削弱,但两段段内氨基酸联系明显增强;(4)蛋白正负电荷间形成的盐桥数量和百分比均降低,尤其在0.3 mol/L NaCl水溶液中的减少更为明显。(5)结果说明,人类神经元钙传感蛋白对溶液NaCl浓度的改变非常敏感,NaCl浓度的微小变化能够引起蛋白关键结构的改变,从原子-分子的视角,为人类神经元钙传感蛋白在不同溶液环境中的结构变化提供理论参考。bBACKGROUND： Human neuronal calcium sensor-1（NCS-1） protein with a high charge is extremely sensitive to solution temperature, but whether the change of ion concentration in the solution can change the protein structure and affect the physiological function has not been reported. OBJECTIVE： To investigate the molecular mechanism of variations of sodium chloride concentration altering conformational dynamics of human NCS-1. METHODS： Through molecular dynamics simulation, the first two minimum energy models（PDB id： 2 LCP） were utilized as the starting states of each independent molecular dynamics simulation of the human NCS-1 protein. After energy minimization, two different initial structures were used to conduct three independent 500 ns molecular dynamics simulations with explicit solvent for human NCS-1 protein at 0.1, 0.3 and 1 mol/L sodium chloride concentration. RESULTS AND CONCLUSION： The slightly high concentration of sodium chloride increased the flexibility of loop L2, simultaneously expanded the global and local structure of NCS-1 protein. Increase in sodium chloride concentration induced loop L3 to adopt a collapsed state and reduced the connectivity between the starting and ending residues of loop L3. N-domain and C-domain interdomain correlation was weakened and the intradomain coupling strengthened. Formation number and the probability of the salt bridges were reduced dramatically, especially at 0.3 mol/L sodium chloride. These findings manifest that human NCS-1 protein is sensitive to the small variation of sodium chloride concentration, which may alter the key factors on protein conformation. Our study may provide the theoretical reference at the atomic structural insights for probing the conformational variations of human NCS-1 protein at the different aqueous solutions.

关 键 词：神经细胞钙离子传感蛋白质类 氯化钠 蛋白质结构 四级 动力学 计算机模拟 组织工程 人类神经元钙传感蛋白 NaCl浓度 结构特性 动态网络分析 盐桥 计算机分子动力学模拟 

分 类 号：R318[医药卫生—生物医学工程]