蛋白质折叠高效模拟方法及折叠病致病机理研究

项目名称： 蛋白质折叠高效模拟方法及折叠病致病机理研究

项目编号： No.11204342

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 物理学I

项目作者： 魏彦杰

作者单位： 中国科学院深圳先进技术研究院

项目金额： 25万元

中文摘要： 蛋白质折叠过程中的结构变异可能导致'折叠病'，比如老年痴呆症、多聚谷氨酰胺疾病等。因此蛋白质折叠研究对于揭示'折叠病'致病机理有重大意义。本项目将研究蛋白质折叠的高效模拟方法；并以多聚谷氨酰胺疾病为例，探索'折叠病'的致病机理。具体内容包括：提出蛋白质侧链的系统研究方法；研究蛋白质折叠高效并行算法；研究多聚谷氨酰胺误叠和聚集的致病机理。其中前两方面工作是本项目中蛋白质折叠高效模拟方法的重要组成部分；该高效模拟方法将被用于研究'折叠病'的致病机理，有如下特点：（1）全面系统分析侧链在蛋白质折叠中的作用；（2）基于圆周统计模型，更准确描述物理量热动力学涨落和涨落关联；（3）蛋白质结构空间高效搜索、正则系综内物理量高效计算及系统状态密度函数高效计算。本项目拟建立的高效模拟方法对于促进我国蛋白质折叠的基础算法研究以及折叠病致病机理的应用研究有着重要意义。

中文关键词： 蛋白质折叠；并行蒙特卡洛算法；蛋白质结构预测；折叠病；药物设计

英文摘要： Protein misfolding leads to many diseases, such as Alzhemizer disease, polyQ diseases, etc. Protein folding research is vital for mechanism study of folding-related diseases. This proposal aims at studying the mechanism of polyQ disease using a new efficient simulation method.In this proposal we will focus on a systematic method for side chain study on protein folding,a new efficient parallel algorithm for protein folding, and mechanism study of polyQ disease using the developed method. The propsed efficient simulation method for protein folding consits of the first two parts, and it will be used to study the mechanism of polyQ disease. The new features of proposed method include: (1) A systematic method for side chain effect study including using hydrogen bond and disulfide bond analysis, disecting energies into side chain to side chain energy, side chain to backbone energy,etc.,(2) Using circular statistics for thermodynamic study of protein folding,(3) A high efficient Wang-Landau sampling algorithm for protein folding which can also compute the thermodynamic canonical averages of physical quantities and the densigy of state of the system. The developed efficient simulation method for protein folding will promote protein research in China, and its role for polyQ disease study will result in more applications

英文关键词： Protein folding；Parallel Mento Carlo Algorithm；Protein Structure Prediction；Folding Disease；drug design