【作者】 魏凯；

【导师】 郭庆祥；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2008， 博士

【摘要】 生物大分子体系的研究能够加深人们对生命过程的认识,也能够提高人类对生物大分子的综合利用。因此深入研究木质素的生物合成的机理以及HDV核酶自切除反应的机理是当前生物物理有机化学、化学生物学、生物医学等领域中最热门的前沿课题之一。但由于实验条件和研究对象的限制,采用量子理论化学方法就显得非常必要。这些课题会为生物质热解为生物油的研究,以及HDV核酶的基因治疗提供了有价值的理论指导。本论文对木质素单体的键离解能、气态电离能、水溶液中的氧化电动势等物理化学性质进行了深入的研究:对HDV核酶自切除反应的机理进行了详细的研究,本文的主要研究工作如下:通过结合密度泛函的方法以及与实验数据,经过对数据的线性拟合,能够精确的预测不同木质素单体的相对和绝对键离解能、气态电离能、水溶液中的氧化电动势,精度达到2 kcal/mol,同时通过木质素单体征水溶液中的氧化电动势的研究,找到了木质素生物合成的反应过程和反应机理。为精确预测酚类化合物的物理化学性质提供了可行性,为木质素的研究提供了有益的理论指导。率先尝试将分子动力学、量子力学反应路径搜索、量子力学与分子力学组合(QM/MM)、自由能微扰、NAC、pK_a、表观活化能等概念相结合应用于HDV核酶的自切除反应机理的研究。我们最终确定了在科学界争论了20多年的HDV核酶自切除反应的机理。为基因治疗肝病毒提供了有益的理论指导。同时这一套方法无论从机理的解释还是从数据的精度上来讲,都将优于以往一种或者两种方法相结合的计算,可以将这一套方法扩展到其他生物大分子体系的研究。拓展了物理有机化学研究方法和研究领域。基于量子化学理论方法的第一性原理,其计算结果是可靠的,同时它不受实验条件的限制,可以解决一些通过实验手段难以解决的问题。本论文的研究成果,会对生物质洁净能源的研究以及HDV核酶的基因治疗提供有价值的基础资料。更多还原

【Abstract】 The researches on Biomacromolecules can deepen our understanding of life science,and also can improve the applications of biomacromolecules. So the researches on the mechanisms of lignin biosynthesis and the mechanisms of self-cleaving reaction of HDV ribozyme are one of the hot directions in biophysical organic chemistry,biochemistry and biomedicine areas.As the limitation of experimental conditions and lack of experimental methods,it is very necessary and important to adopt the quantum theoretical chemistry method.And these works can give some valuable guides on biomass research,and the gene therapies of HDV ribozyme.This dissertation focuses on the BDEs,IPs,Eox of monolignols and the mechanisms of the self-cleaving reaction of HDV ribozyme.The research topics are as follows:Basing on the DFT method and experimental data,via linear fitting we can predict different monolignols’ relevant and absolute BDEs,IPs and aqueous Eox.The precision is within 2 kcal/mol.After the research on the aqueous Eox of different monolignols we have found the mechanisms and procedures of lignin biosynthesis.The can give some valuable information and guides on the research of lignin.We made running on combining MD(Molecular Dynamics),Quantum Mechanism on reaction path search,QM/MM,FEP(Free Energy Perturbation), NAC(Near Attack Conformations),pK_a,apparent activation energy etc. conceptions to research the mechanisms of the self-cleaving reaction of HDV ribozyme.Finally,we found the mechanisms which has been disturbing this area for 20 years.Also this work can give useful guides on the therapies of HDV. Also,this hybrid methods are superior to the traditional methods.So we can extend this method to the researches of other biomacromolecules.This will expand the research area of physical organic chemistry.Theoretical quantum chemical study is reliable because of its first principle.Theoretical studies can resolve the problems which are difficult or inaccurate in experiments.The research result of this dissertation provides valuable and fundamental information to the development of biomass cleaning energy and the gene therapies of HDV ribozyme.更多还原