Integrative approaches for characterizing protein dynamics: NMR, CryoEM, and computer simulations

Proteins are inherently dynamic and their internal motions are essential for biological function. Protein motions cover a broad range of timescales: 10^-14-10 s, spanning from sub-picosecond vibrational motions of atoms via microsecond loop conformational rearrangements to millisecond large amplitude domain reorientations. Observing protein dynamics over all timescales and connecting motions and structure to biological mechanisms requires integration of multiple experimental and computational techniques. This review reports on state-of-the-art approaches for assessing dynamics in biological systems using recent examples of virus assemblies, enzymes, and molecular machines. By integrating NMR spectroscopy in solution and the solid state, cryo electron microscopy, and molecular dynamics simulations, atomistic pictures of protein motions are obtained, not accessible from any single method in isolation. This information provides fundamental insights into protein behavior that can guide the development of future therapeutics.