We are changing every second of every day. We travel around and between our offices and homes, and move our bodies to perform tasks. The proteins and other biomolecules that comprise us are no different. For us, our relevant timescales range from milliseconds to many years and we are conscious of experiences on these timescales. Biomolecules move around and perform their functions on timescales that are generally much faster, occurring between femtoseconds and seconds. To study motions of biomolecules on these timescales is a considerable challenge, but advances over the last 40 years have bought us to the point that we now can start to decipher the atomic goings on of biomolecules on their relevant timescales. In this issue we present an historical perspective on one of the early papers in our field by Lipari and Szabo, which was published in the Biophysical Journal in 1980. This work laid the foundation for the study of internal motions of biomolecules using the model-free approach that is now frequently used to analyze relaxation data measured by nuclear magnetic resonance spectroscopy (NMR) and fluorescence anisotropy. Lipari and Szabo demonstrated how to study the internal dynamics of molecules, where overall rigid body rotational diffusion is separated from the more local internal motions which are described by the order parameter S.
The cover image for this issue of Biophysical Journal includes one of the original figures from the 1980 Lipari and Szabo paper (center) and is complemented by representations of the protein myoglobin, with cones representing the amplitude of internal motion of methyl groups in the interior of the molecule, as inferred from the temperature factors obtained for a room-temperature crystal structure. In representing the molecule within the glassy sphere similar to a marble, we try to capture the concept of the rigid body rotation of the molecule, while with the pink cones we communicate the approximate degree of motion for the atoms. By determining the amplitude of motion in biomolecules on the timescales of ps-ns we discover the degree of flexibility of these entities and try to relate the degree of motion on these timescales to biological function.
The original paper from Lipari and Szabo was followed by two papers by the same authors that described the details of the model free approach. Since then, order parameters have been determined for many different backbone and side chain atoms of various proteins. These studies have illuminated the dynamic nature of biomolecules, which we continue to study at ever increasing spatial and temporal resolution.
– R. Bryn Fenwick and H. Jane Dyson