次级主动运载体传输底物机理的理论研究

项目名称： 次级主动运载体传输底物机理的理论研究

项目编号： No.21203072

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 物理化学

项目作者： 张继龙

作者单位： 吉林大学

项目金额： 22万元

中文摘要： 次级主动运载体蛋白跨膜传输底物的具体机理对于人们深刻认识物质进出细胞的过程和研究细胞代谢具有极其重要的生物学意义。本项目拟通过发展完善CUDA加速的分子动力学模拟程序，结合已有的实验结果，综合运用分子动力学和量化计算方法，对核苷碱基-阳离子同向传输家族成员Mhp1传输底物的完整过程进行深入的理论研究，揭示出底物在蛋白中的具体传输路径及传输过程中与钠离子之间的耦合作用，确定底物传输时蛋白的不同构象状态及彼此间的转化，明晰重要氨基酸残基在底物传输过程中的功能。以此为基础，拓展研究该家族其它成员的底物传输机理。通过比较和分析，总结出该运载体蛋白家族成员的普遍机理，为深入研究这类蛋白的生理功能提供理论指导，并深化人们对次级主动运载体蛋白传输底物具体机理的认识。

中文关键词： 次级主动载体蛋白；底物传输；分子动力学模拟；自由能；外电场

英文摘要： The exact mechanism, by which secondary active transporter protein translocates substrate across the membrane, is of biological significance for the profound understanding of matter's passing through cell membrane and cell's metabolizable action. This project plans to expand and improve the molecular dynamics (MD) simulation program with CUDA acceleration and, by combining with the known experimental results,use MD and quantum chemistry (QM) calculation methods to theoretically investigate the overall substrate-tranport process of the nucleobase-cation-symport-1 family member, Mhp1. The proposal aims to reveal the transport pathway of substrate in protein and its coupling action with cation during the alternating access, determine the protein's conformation states and transformations, and explore the role of the important residues in substrate-transport process. After that,the present project extends the research on the transport mechanism to the other members in the same family. Thus we should summarize the general mechanism of the nucleobase-caion-symport-1 family transporter. Such the project will provide penetrated insight into the physiological function of this kind of transporter proteins and eventually contribute to the related new drug development. Additionally, we can gain a deeper understanding of the

英文关键词： secondary active transporter；substrate transport；molecular dynamics simulation；free energy；external electric field