Strong Adverse Contribution of Conformational Dynamics to Streptavidin-Biotin Binding

Molecular dynamics plays an important role for the biological function of proteins. For protein ligand interactions, changes of conformational entropy of protein and hydration layer are relevant for the binding process. Quasielastic neutron scattering (QENS) was used to investigate differences in protein dynamics and conformational entropy of ligand-bound and ligand-free streptavidin. Protein dynamics were probed both on the fast picosecond timescale using neutron time-of-flight spectroscopy and on the slower nanosecond timescale using high-resolution neutron backscattering spectroscopy. We found the internal equilibrium motions of streptavidin and the corresponding mean square displacements (MSDs) to be greatly reduced upon biotin binding. Based on the observed MSDs, we calculated the difference of conformational entropy ΔSconf of the protein component between ligand-bound and ligand-free streptavidin. The rather large negative ΔSconf value (-2 kJ mol-1 K-1), obtained for the streptavidin tetramer on the...