乙型流感病毒通道蛋白BM2的质子传递机制的理论研究

流感病毒引起的急性呼吸道传染病严重威胁着人类健康并造成重大的经济损失。乙型流感病毒通道蛋白BM2的质子传递机制的研究对阻止乙型流感病毒的传播具有重要的理论和实际意义。目前，还需进一步研究通道激活过程的微观信息和质子传递过程中关键问题，以明确质子传递全过程的微观机制。本课题拟选择BM2作为研究对象，采用分子动力学模拟、QM/MM、PMF等有机结合的多尺度模拟的研究方法，构建BM2通道蛋白的全蛋白三维结构模型，对其质子传递过程开展系统深入的理论研究。考察C端结构域及膜环境对BM2蛋白结构和功能的影响；探究pH值对BM2通道激活的调控机理，确定通道激活的适宜pH范围；明确质子传递的具体方式及其过程中的关键残基，从分子水平阐明该蛋白质子传递的详细机制。本项目的研究成果将为乙型流感病毒的相关实验探索和药物研发提供可靠的理论依据和引导。

While influenza viruses are best known for causing devastating flu pandemics in history, they exert just as much economic and social burden by causing seasonal flu epidemics. It’s very important to prevent the spread of influenza B virus that the proton conduction mechanism of influenza B M2 channel protein is investigated. So far, to make clear the mechanism of proton transfer process，the detailed information of acid activation process and the key problems in the process of proton transfer of the BM2 channel need further study. In our projects, we will construct the full-length structure of BM2 using homology modeling, and carry out a systematic investigation on its proton transfer process by means of multiscale simulation methods including molecular dynamics simulation, QM/MM, PMF. The proposal aims at exploring the effect of C-terminal domain and membrane environment on the structure and function, investigating the pH regulation mechanism of BM2 channel activation and choosing the preferred pH, suggesting the path of proton transfer and the key residues, elucidating the proton transfer mechanism of BM2 in molecular level. Our simulations will provide the reliable thereunder and new cue for the experimental and drug design on the influenza virus B.