蛋白质和多肽链构象的高效采样方法-理论物理专业论文.docxVIP

华 华 中 科 技 大 学 硕 士 学 位 论 文 II II Abstract The computer simulation has been widely used into the study of biomacromolecules such as proteins, however, the poor sampling of conventional molecular dynamics simulation of peptides and proteins is usually considered to be due to numerous local minima in the free energy surface, and during the sampling, it will always stay in these local minima state, yet can’t go to the other states around quickly. Our work begins with the essential composition of proteins, and reviewing the twenty different amino acids making the proteins, then we get back to study the physical properties, including free energy. The next, we study the proteins using the molecular dynamics simulation methods, and then we proposed an efficient double coupling method, At the end, we apply this method to one specific polypeptide to verify our method. At the same time, this paper will show that it is the unfavorable distribution of kinetic energy along special degrees of freedom which should be responsible for this poor sampling. This is due to the decaying form of the kinetic energy distribution along each degree of freedom. To overcome these problems, we modified the kinetic energy distribution by further coupling the environment thermal bath onto the critical order parameters separately and changed the distribution of the kinetic energy along these order parameters to a Gaussian shape. In our work, we apply this method to ALA dipeptide model, and we find that this modified molecular dynamics greatly enhances the sampling behavior in the conformational space and constructs a complete free energy surface along its backbone torsion angles, while conventional molecular dynamics fails to do so. Key words: Molecular dynamics； Generalized coordinate；Conformational sampling； Temperature coupling；Free energy surface III III 目 录 摘 要 I ABSTRACT II 1 绪论 1.1 蛋白质组成 （1） 1.2 蛋白质结构 （7） 1.3 本论文的研究内容 （10） 2 分子动力学模拟理论 2.1 自由能计算 （12） 2.2 恒温分子动力学模拟方法 （13） 2.3 双耦合的采样