| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
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
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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
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