Collective Excitations in Protein as a Measure of Balance Between its Softness and Rigidity

Abstract

In this article, we elucidate the protein activity from the perspective of protein softness and flexibility by studying the collective phonon-like excitations in a globular protein, human serum albumin (HSA), and taking advantage of the state-of-the-art inelastic X-ray scattering (IXS) technique. Such excitations demonstrate that the protein becomes softer upon thermal denaturation due to disruption of weak noncovalent bonds. On the other hand, no significant change in the local excitations is detected in ligand- (drugs) bound HSA compared to the ligand-free HSA. Our results clearly suggest that the protein conformational flexibility and rigidity are balanced by the native protein structure for biological activity.

Ergodicity breaking of iron displacement in heme proteins

“…Since the variance of the force depends on the observation window, softening of vibrations is achieved at the temperature above T d allowing the long-time relaxation of the force autocorrelation func-tion to remain within the observation window. An experimental link to this picture is provided by inelastic x-ray scattering [88][89][90] recording softening of the protein phonon-like modes representing global vibrations. In line with the common observations of the dynamical transition, softening of the protein phonon modes is strongly suppressed in dry samples.…”

Experimental mapping of short-wavelength phonons in proteins

“…Phonon-like collective excitations in proteins have been investigated using inelastic X-ray scattering (IXS). 19 , 20 , 21 , 22 , 23 However, IXS has a limited energy resolution, especially for studying low-frequency collective excitations. 24 Compared with IXS, coherent inelastic neutron scattering (INS) technique is exceptionally suitable for investigating low-frequency collective excitations 24 , 25 and has been applied successfully to study collective density fluctuations in amorphous materials, glasses, or liquids.…”

“…Here we report INS study of a model protein, perdeuterated green fluorescent protein (dGFP), dry and hydrated, to investigate low-frequency intra-protein collective motions on the order of femtoseconds to subpicoseconds. 19 , 20 , 21 , 22 , 28 GFP has a remarkable regular structure that is stable and resistant to unfolding so that even the water molecules on the outside of the barrel form “stripes.” 29 Therefore, GFP is a suitable model system for INS measurements. In our experiment, we observed propagating acoustic 21 , 23 , 28 , 30 , 31 and non-propagating localized 19 , 20 , 21 , 22 modes from both samples.…”

“… 19 , 20 , 21 , 22 , 28 GFP has a remarkable regular structure that is stable and resistant to unfolding so that even the water molecules on the outside of the barrel form “stripes.” 29 Therefore, GFP is a suitable model system for INS measurements. In our experiment, we observed propagating acoustic 21 , 23 , 28 , 30 , 31 and non-propagating localized 19 , 20 , 21 , 22 modes from both samples. Further analysis of such excitations helped us to understand the relations between protein flexibility/softness and its activity from a physical perspective.…”