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

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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.