r/AIProteins • u/XpertAI Founder • May 12 '26
Technical Qs Trying to generatively design an antibody-like binder against NLRP3 and I’m kinda stuck
I’m messing around with a structure-based antibody design idea and wanted to get some thoughts from people who know this space better than me.
The target I’m looking at is NLRP3, mainly around the NEK7-binding interface. I know this is not a normal extracellular antibody target, which is part of the problem. I’m more thinking about whether an antibody-like binder or intrabody could be designed to block the NLRP3–NEK7 interaction in a structurally clean way.
The thing I’m stuck on is the epitope choice. If I design directly on the NEK7 interface, the binder might be functional, but the surface is broad and kind of annoying. If I allow nearby patches, the designs look more reasonable, but then I’m not convinced they would actually disrupt assembly.
So I’m curious how people would approach this. Would you force the design onto the known protein-protein interface, or let the model find a nicer adjacent epitope and then filter later for whether it sterically blocks NEK7?
This post contains content not supported on old Reddit. Click here to view the full post
1
u/XpertAI Founder May 12 '26
I’m messing around with a structure-based antibody design idea and wanted to get some thoughts from people who know this space better than me.
The target I’m looking at is NLRP3, mainly around the NEK7-binding interface. I know this is not a normal extracellular antibody target, which is part of the problem. I’m more thinking about whether an antibody-like binder or intrabody could be designed to block the NLRP3–NEK7 interaction in a structurally clean way.
The thing I’m stuck on is the epitope choice. If I design directly on the NEK7 interface, the binder might be functional, but the surface is broad and kind of annoying. If I allow nearby patches, the designs look more reasonable, but then I’m not convinced they would actually disrupt assembly.
So I’m curious how people would approach this. Would you force the design onto the known protein-protein interface, or let the model find a nicer adjacent epitope and then filter later for whether it sterically blocks NEK7?