Automated tool takes guesswork out of interpreting global structural change in proteins

Time-resolved crystallography is used to study how protein structure changes over time. While this method can capture structure changes occurring on the femtoseconds to seconds timescale, understanding overall structural change in proteins is still tricky. Wickstrand et al. developed a tool to improve the interpretation of protein structural dynamics.

Changes in a protein’s structure are measured as changes in diffraction spot intensities. The typical method for decoding diffraction patterns converts diffraction intensity changes into time-dependent electron density changes with a Fourier transform, and examines these intensity changes by eye. The authors automated the last step of this process.

They wrote a script that finds all electron density changes that have occurred within a protein and correlates them to each other, thereby representing how the whole protein has changed. Author Richard Neutze said correlating electron density changes in one part of a protein with electron density changes in another part can be difficult, even for experienced scientists.

“Instead of scientists picking one or two electron density changes within the protein, now we can see how these changes are happening throughout the whole protein in a way that is much easier to interpret,” Neutze said. “The biggest advantage of this is that it makes the process of interpreting protein structural changes more objective.”

The authors used their tool to interpret time-resolved crystallography data from bacteriorhodopsin, a protein that undergoes structural change when exposed to light. The script evaluated the evolution of protein features from 16 nanoseconds to 1.7 milliseconds.

Next, the authors will apply their tool to other protein systems while also developing additional tools to make the interpretation of protein structural changes more reliable and consistent.

Source: “A tool for visualizing protein motions in time-resolved crystallography,” by Cecilia Wickstrand, Gergely Katona, Takanori Nakane, Przemyslaw Nogly, Joerg Standfuss, Eriko Nango, and Richard Neutze, Structural Dynamics (2020). The article can be accessed at https://doi.org/10.1063/1.5126921 .