The cover image for the May 18 issue of Biophysical Journal shows a comparison of the structures of several alanine-rich alpha-helical proteins as they are pulled apart to reveal the nature of the helix-coil transition, using computational tools. Such steered molecular dynamics simulations are difficult to perform using far-from-equilibrium trajectories because they progressively explore structures far from the typical unfolding pathway. To overcome this challenge, we divide the trajectory into stages using the adaptive steered molecular dynamic (ASMD) simulation method, during which the spread in their energetics is better controlled. We found that alanine-rich peptides exhibit corresponding structures as the helices are stretched apart (as shown in the cover image) and that the corresponding required energetics is additive with the length of the sequence.
While wondering how we would demonstrate our findings within a single image, we were inspired by a recent tweet by Daniel Gezelter suggesting the possible use of a table of contents graphic to make an homage to an album cover of the band Joy Division. Such an idea didn’t seem far-fetched, because Volume 12 Issue 9 of Nature Physics in 2016 did just that. Moreover, Stu Cantrill wrote an editorial in Nature Chemistry in July 2017 celebrating a different band, New Order, by incorporating all the song titles from their album Republic. As the traces of our stretched proteins look like the streams seen in the treads of these covers, we wondered if we could add a note to this musical offering from our Biophysical Journal community.
The image is thus an artistic rendering of a staged mechanical unfolding simulation for several polyalanine peptides with increasing length indicated by the colors with increasing frequency. The pattern of their relative positions, when flattened onto the plane of the cover, illustrates the synchronicity in their relative helical breaks and the correspondence in the behavior reported in our paper. Each plane includes five stages for one peptide showing the unfolding process (from left to right) of the alpha-helix. The snapshots of these peptides were taken using the VMD software of our simulated trajectories and emphasize the transition shared by these helices. By stacking the pulling trajectories for different length peptides together, the cover captures how these various alanine-rich peptides unfold in a similar fashion, and how their helical structure is lost successively in concert.
Through our study and this cover, we highlight the stability of the alpha-helix structure within proteins and the correspondence in their behavior as found in several alanine-rich alpha-helices with different sequences, which also gives insight into the behavior of proteins involving this secondary structure. In doing so, our work provides a precedent that the ASMD method also could be applied efficiently to investigate the interactions within other complex systems.
For more information, please go to https://rh.jhu.edu.
- Yi Zhuang, Hailey R. Bureau, Christine Lopez, Ryan Bucher, Stephen Quirk, Rigoberto Hernandez