#3D RNA structure prediction haunts me constantly

[splicejunction]

hello sorry if this is weird but i sort of remember you saying you work with selex (?) i’m part of a team of undergrads rn working on building aptasensors only we don’t have the money for selex lol 💀 do you know of any cheaper ways (preferably computational) we can use for selection and optimisation

not weird at all science asks are my favorite type of ask to receive for real :D

I'm assuming you're talking about RNA aptamers, I have never used any computational methods for designing RNA aptamers/aptasensors myself. I did a quick search and I found this paper:

In silico selection of RNA aptamers, Nucleic Acids Research, https://doi.org/10.1093/nar/gkp408

Our approach consists of three steps: (i) selection of RNA sequences based on their secondary structure, (ii) generating a library of three-dimensional (3D) structures of RNA molecules and (iii) high-throughput virtual screening of this library to select aptamers with binding affinity to a desired small molecule.

I can't speak to how well this works because I haven't used it, but it looks like it worked for them. there's also this review apparently:

In-Silico Selection of Aptamer: A Review on the Revolutionary Approach to Understand the Aptamer Design and Interaction Through Computational Chemistry, https://doi.org/10.1016/j.matpr.2019.11.185 (paywalled but pdf here)

designing aptamers in silico from random sequence relies on RNA 3D structure prediction which is.... getting better, but we don't really have an equivalent of Alphafold yet for RNA structure. designing aptamers computationally would require simulating RNA structure and complexation with ligands and I just don't know if our current 3D structure prediction methods are good enough for that, but you could give it a try, & if you do you let me know how it goes!!

I would love to hear more about your project like what ligand you're trying to bind & what aspects of SELEX are cost-prohibitive (do you have any budget for wet-lab work/materials?)