From Cricket Bans to Binding Pockets: Building Mental Models for Viral Glycoproteins in VR
From Cricket Bans to Binding Pockets: Building Mental Models for Viral Glycoproteins in VR The notification hit my phone at 11:47 PM on a Tuesday. EU bans house cricket protein in food products — EFSA cites insufficient safety data on allergen cross-reactivity. I stared at the screen, thumb hovering. Three years of grant proposals, late-night sequencing runs, and that one spectacular failure with…
At 11:47 PM on a Tuesday, my phone notification interrupted my thoughts. The European Food Safety Authority (EFSA) had banned house cricket protein from food products, citing insufficient safety data on allergen cross-reactivity. This news brought back memories of three years of grant proposals, late-night sequencing work, and a failed cryo-EM experiment involving cricket proteins.
My lab focuses on viral glycoproteins, not insects, but the EFSA panel's reasoning using structural homology between invertebrate tropomyosin and cricket allergens reminded me of my own struggles with homology models.
Three years ago, I stood in front of a Titan Krios electron microscope, working on a novel Orthomyxovirus glycoprotein from bat guano in Yunnan. Despite six months of optimization and weeks of grid screening, the 3D structure remained elusive. The receptor-binding domain and fusion peptide remained invisible in the final map, leaving a ghost density that hinted at a flexible structure.
The EFSA panel built a mental model based on static snapshots and predicted structures, considering the homology sufficient for regulation. However, they missed the dynamic nature of viruses, which transition between states rather than remaining static. Influenza and SARS-CoV-2 have well-documented examples of dynamic structures, and the epitopes they target only exist transiently.
I had tried to convey this concept to collaborators using visualization tools, but they preferred knowing the coordinates of the "open state" for compound docking. The VR headset, purchased for exploratory visualization, finally sat untouched for six months. The cricket ban notification sparked an idea: what if EFSA could experience the structural homology in virtual reality?
I loaded the VR headset and installed a Unity-based molecular viewer that streamed MD trajectories from the cluster. As I entered the prefusion trimer of the bat virus glycoprotein, the nausea disappeared, replaced by a sense of immersion. I walked through the receptor-binding domain, observing the breathing motion of the hinge region. The elusive pocket, previously invisible, materialized as a transition between conformations.
Excited by this discovery, I shared my findings with my postdoc, who had previously worked on insect allergens. Together, we explored the AlphaFold2-predicted cricket tropomyosin dimer and the predicted IgE epitope in the dimer interface. Our computational core's student from Wageningen demonstrated how the epitope unfolds during digestion, revealing its dynamic nature that static structures could not capture.
This VR experience highlighted the importance of capturing structural transitions, not just static snapshots, in understanding viral structures and their interactions. The cricket ban, initially concerning, became a catalyst for a new perspective in our structural biology research.
Written by urgent.news from Dev.to's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
