Database construction for the effect of metal ions on nucleic acid folding

有关核酸(DNA和RNA)的各种折叠模式的信息是非常重要的，因为它是许多研究和广泛领域中研究不可或缺的信息。然而，环境因素，如金属离子的种类和浓度、共溶质、pH等对核酸折叠的影响却知之甚少，本研究的目的是建立环境因素对核酸折叠进入高阶结构的能量贡献数据库。在开发了所需的能量数据库后，人们可以很容易地预测在各种不同条件下核酸的杂交效率。为实现这一目标，计划了一个三步走的战略。具体来说，每个步骤如下：(1)详细分析金属离子对非常有趣的功能核酸的特定结构和功能的影响。(2)参数的开发和数据库…的建设更多的是为了预测金属离子对核酸折叠为双链、三链和四链的能量贡献。(3)利用能量数据库设计了最适合检测特定结构的方法，如单核苷酸多态(SNP)或特殊的三维结构，量化了平行/反平行双链、平行/反平行三链和G-四联体/I-基序四链结构的稳定性与pH、金属离子和共溶质的依赖关系。此外，还对这两种结构的组合效果进行了评估。通过查阅能量参数数据库，兼性结构变化能够按预期进行设计。例如，改变金属离子浓度可以引起核酸构象的剧烈变化，即d(G_4T_4G_4)的反平行G-四链结构向平行方向转变。我们在这项研究中获得的能量参数和结果数据库将是许多研究核酸的研究人员不可或缺的参考。较少

The information about various folding patterns of nucleic acids (DNA and RNA) is very important because it is indispensable for many researches and studies in vast fields. However, little is known about the effect of environmental factors, e.g. kinds and concentration of metal ions, co-solutes, pH and so on, on the nucleic acid folding.The aim of this study is construction of database for the energetic contribution of the environmental factors to the folding of nucleic acids into the higher-order structure. It is expected that one can easily predict the hybridization efficiency of the nucleic acids under various different conditions after the development of the desired energetic database. A three-step strategy was planned for achieving the goal. In concrete, the each step was as follows : (1) Detailed analysis of the effect of metal ions on the specific structures and functions of very interesting functional nucleic acids. (2) Development of parameters and construction of the database … More to predict the energetic contribution of the metal ions to the nucleic acid folding to duplexes, triplexes, and quadruplexes. (3) Design of the most suitable method for detection of specific structures, such as single nucleotide polymorphism (SNP) or special three-dimensional structures, by means of the energetic database.As the result, the pH, metal ion, and co-solute dependency of the stability for many structures of parallel/anti-parallel duplex, parallel/anti-parallel triplex and G-quartet/i-motif quadruplex was quantified. Furthermore, the combinational effect of the conditions was evaluated in either structure. By referring the energetic parameter database, facultative structural changes were able to design as expected. For example, a drastic conformational change of a nucleic acid, i.e. antiparallel G-quadruplex structure of d(G_4T_4G_4) to parallel orientation, could be induced by altered metal ion concentration. Our energy parameters and the resulting database obtained in this study would be the indispensable reference for numerous researchers dealing with nucleic acids. Less