Femtosecond X-ray snapshots reveal correlated displacements of specific distal atoms in a protein crystal

Abstract

Protein dynamics is shaped by interactions between thermal fluctuations, external forces, and molecular structures. Thermal fluctuations have high frequencies and are hence very challenging to quantify. We were able to record femtosecond X-ray diffraction snapshots and determine atomic displacements of crystalline bovine trypsin atoms either in the native steady state or in a transient state initiated by a short THz pulse, the results of which were interpreted with numerical simulations. In the absence of THz pulses, specific distal atoms exhibited correlated movements. Under the influence of THz fields, numerical simulations demonstrated a slight enhancement of displacement correlations. The experimental results revealed a contrasting response to short THz pulses, where the measured displacements were not solely determined by the atom position, but also influenced by the atomic type. These findings call for a reinterpretation of the dynamic properties inherent in folded protein structures and the physical principles behind the formation of protein assemblies. To this end, a theoretical model was developed for lattice deformations and local excitations entraining a (squeezed) coherent steady state, explaining the emergence of atom correlations. The model accounts for the magnitudes of atomic displacements and fluctuations through a balance between harmonic and anharmonic coupling forces.

Deciphering peptide-protein interactions via composition-based prediction: a case study with survivin/BIRC5

“…Departing from structural information, our study initially focused on atom displacement analysis in folded proteins. The observation that atoms with similar chemical properties exhibit shared displacement patterns [72,73] led to a dynamic model in second-quantization, revealing coherent motion of phononic and dipolar collective excitations within the protein crystal [74]. This coherence extends between different proteins over intermolecular distances, involving identical functional groups.…”