The process was super smooth to be honest -- no complaints here!

Good to hear, Kresten -- we think the method is very cool (and plan to use it for some projects here soon)! Plenty of room to explore using the foundation you've built...

Thanks for encouraging this kind of thing more broadly @fraserlab.com, and for paving the way with another previous pre-review (pre-pre-review? 🤔) of the same preprint @stephanieaw.bsky.social !

Thx! Next time you're in Big Apple City or I'm in Beantown for sure...

Gift link
www.nytimes.com/2025/07/22/s...

We hope qFit + RINFAIRE is a useful comp struct bio pipeline for exploring how evolution has tinkered w/ allosteric wiring in prot fams, how collective dynamics "evolve" during iterative protein design, & how small-mol frag hits from X-ray screens tap into "nervous systems" of allosteric proteins!

To validate RINFAIRE, we showed that fxnally impactful mutations from many PTPs are enriched near our network residues.

We also experimentally mutated residues that had varying seq conservation but were very interconnected per RINFAIRE. All muts altered catalysis -- & one surprisingly enhanced it!

We used RINFAIRE to map allosteric (re)wiring for the entire PTP enzyme family.

We found that PTPs have similar wiring that responds dynamically to catalytic motions & active-site vs. allosteric ligands, but differs among fxnally distinct PTPs.

All PTP supp files here: zenodo.org/records/1542...

Enter RINFAIRE (Residue Interaction Networks From Alternate conformations In RElated structures)! 🏰 🐴 🍗

RINFAIRE builds "dynamic RINs" from qFit models, aligns them, and quantitatively compares them, including normalization, subsetting, etc.

The code is available here: github.com/keedylab/rin...

We hypothesized that deviations from the avg struct may differ among homologs & diversify fxns e.g. catalysis & allostery.

Crystallographic alt confs from qFit offered a foothold, but we needed new tools to model networks of interacting alt confs and compare btw many related protein structures...

Protein design & fragment screening: two great flavors combined! Super cool... Congrats, all y'all!