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Stability and dynamics of DNA molecules in solution and near material surfaces

溶液中和材料表面附近 DNA 分子的稳定性和动力学

基本信息

批准号：
99265244
负责人：
Professor Dr. Dietmar Blohm
金额：
--
依托单位：
Jihočeská univerzita v Českých Budějovicích
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/99265244?language=en
关键词：
Stability dynamics DNA molecules solution

项目摘要

Binding of single-stranded DNA oligonucleotides to complementary strands is widely used for sequence-specific recognition of DNA. It forms the basis for the parallel detection of many nucleic acid molecules using microarrays of oligonucleotides covalently attached to a solid support. Prediction of DNA hybridisation efficiency mostly based on nearest neighbour (NN) models is still often unreliable because it is not only influenced by the DNA sequence but also by hybrisiation conditions and the presence of linker molecules and the solid surface. The realistic prediction of hybridisation efficiency requires a deeper understanding of the dynamics of DNA duplexes in solution and near solid surfaces at molecuar detail. Aim of the project is to use a combined experimental and molecular dynamics simulation approach to study the relation of hybridisation behavior of oligonucleotides and DNA conformational dynamics in solution and near surfaces. DNA duplexes with same base content (and similar calculated stability based on NN-models) but significantly different hybridisation efficiency will be studied. MD simulations will be performed on duplexes and single-stranded DNA in the absence and presence of a surface. It is expected that duplexes with AT(adenine/thymine) rich termini show increased fraying and conformational dynamics at the duplex termini which results in the breakdown of NN- models to predict duplex stability and in altered interactions with surfaces. A surface layer force field model will be developed in collaboration with the Czeck partner (Prof. Sip) and the interaction of DNA structures with solid surfaces will be studied together with the Czech group using molecular mechanics and quantum-mechanical approaches.

单链DNA寡核苷酸与互补链的结合广泛用于DNA的序列特异性识别。它形成了使用共价连接到固体支持物的寡核苷酸微阵列平行检测许多核酸分子的基础。主要基于最近邻（NN）模型的DNA杂交效率的预测仍然经常是不可靠的，因为它不仅受DNA序列的影响，而且受杂交条件以及接头分子和固体表面的存在的影响。杂交效率的现实预测需要更深入地了解DNA双链体在溶液中和近固体表面的分子细节的动力学。本研究的目的是利用实验和分子动力学模拟相结合的方法来研究溶液和近表面中寡核苷酸的杂交行为与DNA构象动力学的关系。将研究具有相同碱基含量（和基于NN模型的相似计算稳定性）但杂交效率显著不同的DNA双链体。将在不存在和存在表面的情况下对双链体和单链DNA进行MD模拟。预期具有富含AT（腺嘌呤/胸腺嘧啶）末端的双链体在双链体末端处显示增加的磨损和构象动力学，这导致预测双链体稳定性的NN模型的崩溃和与表面的改变的相互作用。将与Czeck合作伙伴（Sip教授）合作开发表面层力场模型，并将与捷克小组一起使用分子力学和量子力学方法研究DNA结构与固体表面的相互作用。