Diffusion and internal dynamics of proteins in crowded solutions

Protein function is determined through the interplay of structure, dynamics and the aqueous, but crowded cellular environment. We present a comprehensive study accessing the full hierarchy of protein dynamics in solutions, e.g. vibrations, interdomain motions and diffusion of the entire protein. Quasi-elastic neutron and dynamic light scattering experiments are performed and compared to theoretical predictions. In crowded solutions, both self diffusion $D_s$ and collective diffusion $D_c$ of protein solutions are well described by colloidal concepts, with $D_s$ reduced to $20 \%$ at $\approx 20 \%$ volume fraction [1,2]. Separating the motion of the entire protein molecule, the internal motions are accessed under native conditions [3]. We studied the dynamics before, during and after thermal denaturation, supporting the notion of protein unfolding with subsequent chain entanglement. While long-range motions are {\it reduced} in the denatured state, the local flexibility of side chains is found to be {\it enhanced}. The frameworks enable further experimental access to the relation of protein function and dynamics at fast time scales. [1] F. Roosen-Runge et al., PNAS 108 (2011) 11815; [2] M. Heinen et al., Soft Matter 8 (2012) 1404; [3] M. Hennig et al., Soft Matter 8 (2012) 1628