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

单链DNA寡核苷酸与互补链结合被广泛用于DNA序列特异性识别。它形成了使用共价连接到固体载体上的寡核苷酸微阵列来并行检测许多核酸分子的基础。DNA杂交效率的预测大多基于最近邻(NN)模型，因为它不仅受DNA序列的影响，而且还受杂交条件、连接物分子和固体表面的存在的影响。对杂交效率的现实预测需要更深入地了解DNA双链在溶液和近固体表面的分子细节动力学。本项目的目的是利用实验和分子动力学相结合的模拟方法来研究寡核苷酸在溶液和近表面中的杂交行为与DNA构象动力学的关系。具有相同碱基含量(以及基于神经网络模型计算的相似稳定性)但杂交效率显著不同的DNA双链将被研究。分子动力学模拟将在没有表面和存在表面的情况下对双链和单链DNA进行。预计富含AT(腺嘌呤/胸腺嘧啶)末端的双链在双链末端表现出更多的磨损和构象动力学，这导致预测双链稳定性的神经网络模型崩溃，并改变与表面的相互作用。将与切克伙伴(Sip教授)合作开发表层力场模型，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。

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.