Mike Filius

Cheap Computation of Small Peptide Binders

Interested in computationally predicting peptide binders to a protein-of interest?

Check out this @science.org blog post by @dereklowe.bsky.social on the work by @sebastianpomplun.bsky.social of our @led3hub.bsky.social on predicting peptide binders using BindCraft.

www.science.org/content/blog...

Evaluating BindCraft for Generative Design of High-Affinity Peptides Discovering high-affinity ligands directly from protein structures remains a key challenge in drug discovery. BindCraft is a structure-guided generative modeling platform able to de novo design miniproteins with a high affinity for a large set of targets. While miniproteins are valuable research tools, short peptides offer substantially greater therapeutic potential. However, given their lack of stabilized tertiary structures, de novo generation of functional peptides is a remarkable challenge. Here, we show that BindCraft is able to generate high affinity peptides, solely based on target structure, with remarkable success rates. For the oncoprotein MDM2, BindCraft generated 70 unique peptides; 15 were synthesized, and 7 showed specific binding with nanomolar affinities. Competition assays confirmed site-specific binding for the intended target site. For another oncology target, WDR5, six out of nine candidates bound the MYC binding WBM site with submicromolar affinity. Bindcraft’s high fidelity structure prediction enabled one shot peptide optimization via rational chemical modification, improving the potency of one WDR5 binder by 6-fold to a KD of 39 nM. BindCraft also generated candidate peptides for targeting PD-1 and PD-L1. However, none of the tested peptides showed detectable binding. Together, these results establish a first evaluation of BindCraft for peptide binder prediction. Despite remaining limitations, this tool shows the potential to rival display technologies in delivering high-affinity ligands for therapeutic development.

Looking for a high-affinity #peptide binder for your favorite target?

According to the newest paper by the group of @sebastianpomplun.bsky.social, the software tool #BindCraft allows you to predict such binders with high success rates.

pubs.acs.org/doi/10.1021/...
#ChemSky #ChemBio #DrugDiscovery

Generative Design of High-Affinity Peptides Using BindCraft Discovering high-affinity ligands directly from protein structures remains a key challenge in drug discovery. We applied BindCraft, a structure-guided generative modeling platform, to de novo design o...

"Generative Design of High-Affinity Peptides Using BindCraft".

New @biorxivpreprint.bsky.social by the group of @sebastianpomplun.bsky.social of our @led3hub.bsky.social!

www.biorxiv.org/content/10.1...

Cc: @leidenscience.bsky.social, @unileiden.bsky.social

Thanks for sharing our work Stephan!

Check out our latest work:
“Generative design of high-affinity peptides using BindCraft” now on bioRxiv

BindCraft generates peptide binders for MDM2 and WDR5 with nanomolar affinities—further enhanced through rational chemical modifications.

Huge thanks to the amazing team putting this together! 🙌

Generative Design of High-Affinity Peptides Using BindCraft

www.biorxiv.org/content/10.1...

Was great showing our work on single molecule analysis of aptamer-protein interactions at the #LED3Symposium

A PhD position is open for this year. A candidate should have a background in programming skills.

🚨New paper alert! 🚨

Today in @naturesmb.bsky.social we uncover how the oxidoreductase PYROXD1 protects the human tRNA ligase complex against oxidative stress. A great collaboration between the @martinjinek.bsky.social lab and the Javier Martinez lab.

www.nature.com/articles/s41...

New year. New social media platform #BlueSky and a New job as a postdoc @unileiden.bsky.social Super excited to start this next adventure.

Happy new year to all!

Great stuff from a great friend @lloeff.bsky.social on the underlying mechanism of the Shedu anti-phage defense system. #HappyReading :)

Congrats Tim and team! Very cool to see you guys lowering the bar for people to use single molecule tech :) keep up the good work!

Hi Johannes, great stuff! Could you add me in the group?