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Time Resolved THz Calorimetry explores Molecular Recognition Processes

Periodic Reporting for period 3 - THZCALORIMETRY (Time Resolved THz Calorimetry explores Molecular Recognition Processes)

Reporting period: 2019-10-01 to 2021-03-31

Advances in THz technology will make it possible to develop strong, ultrafast THz sources in the frequency range up to 10THz that allow for the detection of frequency-resolved transient low frequency spectra of biological samples with μsec or even nsec time resolution. We will correlate the transient THz spectra with changes in the entropy and enthalpy, both experimentally and theoretically.

THz-calorimetry is a revolutionary approach that enables the characterization of individual enzymes and their mode of binding to their substrates and endogenous inhibitors with great precision. Such precision is required to map potential allosteric small molecule drugs targeting the non-homologous enzyme surface away from the structurally homologous active site.

- Implement an experimental setup that is able to monitor low frequency spectra (0-300 cm-1) of the solvated protein during molecular recognition
- Introduce THz-calorimetry by combination of novel experimental and simulation methods
- Apply THz-calorimetry to study catalytic reactions and molecular binding events
- Unravel the role of the solvent for enzymatic catalysis
We have set-up a high power, rapid scanning KITA system and improved the signal-to-noise ratio considerably.
We have extended the frequency range by a plasma source and are setting up a strong THz source in the frequency range up to 10THz.
We have developed a library of matrix metalloproteases (MMPs).
We have developed simulation tools to adequately describe the low frequency spectral region.
We have developed a new method to extract thermodynamic properties from low frequency vibrational spectra experimentally and in molecular dynamics simulations.
We are convinced that THz calorimetry will open new horizons and will have a broader impact as a cutting-edge biophysical tool to investigate protein-ligand binding.