Probing DNA properties by a combination of molecular modelling and EPR spectroscopy (OGANESYANU16SF)

The knowledge about structures and conformational dynamics of nucleic acids in DNA is crucial to understand their biological functions (e.g. DNA reparation and replication mechanisms), including interactions with proteins and lipids. Such knowledge is important for the drug development strategies. Electron Paramagnetic Resonance (EPR) with paramagnetic spin probes is particularly suitable spectroscopic technique to study the dynamics and conformational changes in complex molecular systems such as DNA.

Recent research undertaken in the Oganesyan group has demonstrated that EPR in combination with Molecular Dynamics (MD) simulations are able to offer a detailed information about the molecular motions and structure in complex soft matter and bio-molecular systems [1, 2]. Such a combined MD-EPR simulation approach greatly simplifies the interpretation and analysis of experimental spectra providing a new level of detail in molecular motions and order. Our MD-EPR methodology has been successfully applied to characterise liquid crystals [3, 4] and proteins [2, 5]. This included the ability to characterise protein motions and molecular behaviour across the critical points of the phase transitions in liquid crystals.

The goal of this PhD project is apply a combined MD-EPR approach to DNA systems. It will involve developing computer models of spin labelled DNA molecules as well as DNA-protein and DNA-lipid complexes and testing them against experimental EPR measurements carried out under different conditions.
The project will combine state-of-the-art MD modelling techniques with EPR and will provide a PhD student with the unique opportunity for training in both computer modelling and experimental methods.