复杂受限体系中蛋白质折叠行为的动力学模拟研究

项目名称： 复杂受限体系中蛋白质折叠行为的动力学模拟研究

项目编号： No.21204078

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 高分子科学

项目作者： 姜舟婷

作者单位： 中国计量学院

项目金额： 25万元

中文摘要： 蛋白质分子的折叠过程与所处的外部环境密切相关，是一个受到热力学和动力学双重制约的过程。蛋白质分子在复杂受限体系中的折叠行为研究，对认识生命现象、控制生物过程乃至发明新型药物和诊疗方法，都有着重要的意义。本项目拟采用结合粗粒化和全原子模型的副本交换分子动力学模拟，对蛋白质在复杂受限体系中折叠的动力学过程和热力学性质进行研究。通过计算机模拟和理论分析，达到以下目标：(1)建立一套较完整的研究蛋白质在复杂受限体系中折叠行为的理论方法和模型，包括确立复杂受限空间的势能函数表达式、优化算法、提供有效的结构分析手段。(2)揭示受限空间结构和相互作用方式与蛋白质稳定构型的内在联系。(3)阐明蛋白质在复杂受限体系中折叠过程的物理图像。通过上述研究，深入理解蛋白质的折叠机理，为蛋白质三维结构的预测、功能分析、以及药物设计提供理论依据。

中文关键词： 蛋白质折叠；分子伴侣；受限体系；计算机模拟；

英文摘要： Protein folding is an important and challenging problem in molecular biology. Experiments indicate that the protein folding processes in the crowded cell controlled by both thermodynamic and kinetic effects strongly depend on its local environmental conditions. It is well known that the folding process of certain proteins in vivo requires the assistance from molecular chaperones providing the confined nanocage. Furthmore, some illnesses such as Parkinson's disease, Kreutzfeld-Jacob syndrome and mad cow disease are treated as the result of toxic protien misfolding in the cellular environment. Therefore, the investigation of protein folding behaviors in the complex confinement is significant for understanding the nature of life. The current research proposal carried out numerical analysis and computer simulations aspires to provide the theoretical support for the comprehension of protein folding process under the confined system. The replica-exchange strategies by coupling coarse grained and all-atomistic molecular dynamics simulations will be applied. The anticipated results achieved by computer simulations and theoretical studies are specified as follows (1) To establish the theoretical approach and molecular model concerning the improved expression of confining potential, optimized algorithm, and effective para

英文关键词： Protein Folding；Molecular Chaperones；Confined System；Computer Simulation；