Investigating biomolecular structure, dynamics and intermolecular interactions with 2D-IR and T-jump spectroscopy

Speaker: Professor Neil Hunt, University of York


Professor Neil Hunt, University of York

Research in the NTH group uses ultrafast two-dimensional infrared (2D-IR) spectroscopy to determine the role of fast structural and solvation dynamics in biomolecular processes, ranging from ligand binding to proteins and DNA to the reactions that occur in the active sites of enzymes.

Ultrafast 2D-IR spectroscopy is the infrared equivalent of powerful multidimensional NMR spectroscopy methods in that it employs a sequence of infrared laser pulses to spread the IR absorption spectrum of a sample over a second frequency axis. The result is that the traditional IR absorption spectrum appears along the diagonal of the 2D-IR plot while the off-diagonal region contains peaks that report on couplings or energy transfer between vibrational modes. These peaks provide new information relating to molecular structure and dynamics. Combining this information with the high time resolution of 2D-IR (~ 100 fs) allows experimental visualisation of H-bond motion, dynamic conformational fluctuations of proteins or DNA. By linking ultrafast IR spectroscopy methods to lasers that can initiate a photochemical reaction or cause a fast rise in temperature of the sample we have been able to observe processes such as the melting of double stranded DNA in real time.

Examples of our work include applications of 2D-IR spectroscopy to detect the dynamics of water molecules in enzyme active sites that may play a part in their function and to understand the role of water motion in the action of synthetic catalytic systems that mimic biological molecules. We have also examined how protein structural dynamics could contribute to mechanisms of antimicrobial resistance and examined the structural and dynamical implications of ligand binding to DNA.

Recently, we have begun to explore new directions involving the application of 2D-IR to analytical problems, showing that 2D-IR can be used to analyse the protein content of biofuid samples and performing proof-of-concept 2D-IR screening experiments acquiring >2000 2D-IR spectra of DNA-ligand complexes and categorising them using novel data analysis tools.

NTH collaborates closely with scientists at STFC Rutherford Appleton Laboratory’s (RAL) Central Laser Facility and this has led to the development of 2D-IR instruments on three different RAL spectrometers that are available to the wider UK research community.