When I’m not postdoc-ing, as part of my job I’m also involved with teaching at the Doctoral Training Centre here in Oxford. I mainly teach the first-year students of the Systems Approaches to Biomedical Science CDT – many members of this group are doing (or have done) their DPhils through this program (including myself!). Recently, I and some other OPIGlets were responsible for two modules called Structural Biology and Structure-Based Drug Discovery, and as part of those modules we arranged a practical session on 3D printing.

Most of the time, the way we ‘see’ protein structures is through a computer screen, using visualisation software such as PyMOL. While useful, these virtual representations have their limitations – since the screen is flat, it’s difficult to get a proper feel for the structure¹, and seeing how your protein could interact and form assemblies with others is difficult. Physical, three-dimensional models, on the other hand, allow you to get hands-on with your structure, and understand aspects of your protein that couldn’t be gained from simply looking at images. Plus, they look pretty cool!

This year, I printed three proteins for myself (shown in the photo above). Since my most recent work has focused on transmembrane proteins, I felt it was only right to print one – these are proteins that cross membranes, usually to facilitate the transport of molecules in and out of the cell. I chose the structure of a porin (top of the photo), which (as the name suggests) forms a pore in the cell membrane to allow diffusion across it. This particular protein (1A0S) is a sucrose-specific porin from a type of bacteria called Salmonella typhimurium, and it has three chains (coloured blue, pink and purple in the printed model), each of which has a beta barrel structure. You can just about see in the photo that each chain has regions which are lighter in colour – these are the parts that sit in the cell membrane layer; the darker regions are therefore the parts that stick out from the membrane.

My second printed model was the infamous Zika virus (bottom right). Despite all the trouble it has caused in recent years, in my opinion the structure of the Zika virus is actually quite beautiful, with the envelope proteins forming star-like shapes in a highly symmetrical pattern. This sphere of proteins contains the viral RNA. The particular structure I used to create the model (5IRE) was solved using cryo-electron microscopy, and required aligning over 10,000 images of the virus.

Finally, I printed the structure of a six-residue peptide, that’s probably only interesting to me… Can you tell why?!²

1 – However, look at this link for an example of looking at 3D structures using augmented reality!

2 – Hint: Cysteine, Leucine, Alanine, Isoleucine, Arginine, Glutamic Acid…