Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein-molecule interactions, and has wider implications for biochemical reactivity and biological function.
Underdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low-frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk.
We describe the use of a range of modern spectroscopic techniques—from terahertz time-domain spectroscopy (THz- TDS) to high dynamic-range femtosecond optical Kerr-effect (OKE) spectroscopy—to study the interaction of proteins, peptides, and other biomolecules with the aqueous solvent. Chemical reactivity in proteins requires fast picosecond fluctuations to reach the transition state, to dissipate energy, and (possibly) to reduce the width and height of energy barriers along the reaction coordinate. Such motions are linked with the structure and dynamics of the aqueous solvent making hydration critical to function. These dynamics take place over a huge range of timescales: from the nanosecond timescale of diffusion of water molecules in the first solvation shell of proteins, picosecond motions of amino-acid side chains, and sub-picosecond librational and phonon-like motions of water. It is shown that a large range of frequencies from MHz to THz is accessible directly using OKE resulting in the reduced anisotropic Raman spectrum and by using a combination of techniques including THz-TDS resulting in the dielectric spectrum. Using these techniques, we can now observe very significant differences in the spectra of proteins in aqueous solvent in the 3-30 THz range and more subtle differences at lower frequencies (10 GHz-3 THz
The dynamics of biomolecules can often be accessed and analysed at terahertz frequencies. Here, we use terahertz optical Kerr-effect (OKE) spectroscopy to probe a range of biological molecules in aqueous solution and demonstrate sensitivity to conformation and solvation
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