Unveiling terahertz dynamics of biomacromolecules in solutions

Research Project, 2025 – 2029

This project aims to enable probing picosecond spectroscopic signatures of proteins and other bio-macromolecules like RNA in solution, thereby giving access to long range structural vibrations of the proteins’ backbone, predicted to be linked to the enzymatic function. Picosecond spectroscopic signatures of proteins have remained inaccessible due to the technological challenges to generate terahertz waves, strong absorption in water, and a broad continuous vibrational density, which prevents the resolution of distinct resonance features. Most advances in the field have been based on terahertz dielectric spectroscopy, using proteins in artificial conformations to minimize water absorption, which imposes restrictions on their molecular dynamics, and of concern in studies of enzymatic reactions. I propose to combine the latest technological advancements of terahertz electronics, paved by space and atmospheric sciences, and molecular alignment techniques of proteins in solution. Ultra-sensitive frequency domain heterodyne electronic instrumentation has demonstrated superior dynamic range and signal to noise ratio. This, combined with a coherent response of all molecules, enabled by molecular orientation techniques, and polarization dependent measurements, will provide sufficient contrast for picosecond spectroscopic signatures to be resolved in solution. This project will open a new spectral window for the understanding of protein dynamics and biologically relevant processes.