Terahertz underdamped vibrational motion governs protein-ligand binding in solution

Abstract

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.

Perspective: Watching low-frequency vibrations of water in biomolecular recognition by THz spectroscopy

“…More recently, Wynne and coworkers reported a low frequency spectrum of a solvated protein-ligand binding complex by using sensitive femtosecond OKE spectroscopy. 41 In order to obtain the solvated protein spectrum, they subtracted the solvent spectrum from the spectrum of the lysozyme solution and claimed the observation of delocalized underdamped vibrational modes in the terahertz frequency domain that blue-shift after inhibitor binding.…”

Terahertz optical measurements of correlated motions with possible allosteric function

“…Not only have the CATM measurements indicated this, but recent optical Kerr effect measurements of lysozyme solutions have found a broad Raman active resonance near 68 cm −1 that is sensitive to inhibitor binding (Turton et al 2014). We now comment on several important aspects of the measurements and calculations.…”

Radiofrequency and microwave interactions between biomolecular systems

“…Actually, several experiments [29-31, 31, 32] and theoretical arguments [33][34][35][36] favor the possibility of underdamped vibrational modes of large biomolecular structures within the higher radiofrequency and THz regions. Prospective research lies in experimental quantification of damping of the radiofrequency vibrational modes using sophisticated spectroscopy techniques such as those exploiting high resolution Brillouin scattering [37], inelastic slow neutron scattering [38], nonlinear optical Kerr-effect pump-probe spectroscopy [32], extraordinary acoustic Raman spectroscopy [39,40] and others.…”