Have you ever wanted to design protein binders with ease? Today we present 𝑩𝒊𝒏𝒅𝑪𝒓𝒂𝒇𝒕, a user-friendly and open-source pipeline that allows to anyone to create protein binders de novo with high experimental success rates. @befcorreia @sokrypton

biorxiv.org/content/10.110… With Lennart Nickel, we designed binders against a range of challenging targets such as cellular receptors, allergens, and CRISPR-Cas9. With BindCraft, we achieved success rates ranging from 24.5% to 100%, while screening only a handful of binders.

THEY SAID WE COULDN'T DO IT........well, no one actually said that. But in our updated manuscript with @CasperGoverde, @GoldbachNico, and @befcorreia we show you can now design soluble analogues of membrane proteins with preserved functional features!

biorxiv.org/content/10.110…
While fixing functional sites during design, we can recapitulate complex interaction sites, such as the Clostridium perfringens enterotoxin binding site on claudins and maintain toxin binding in solution with affinities comparable to its membrane counterpart.

I decided to release a couple of figures from my PhD thesis, perhaps they might be useful to someone! First off is a remake of the famous Makarova et al. 2020 CRISPR classification. This one also includes a schematic of the targeted nucleic acid. Next off we have structural renderings and domain schematics of Class 2 effectors released at the time of writing (missed Cas12k then). PDBs: 6O0Z, 6I1K, 5U30, 6NY2, 7C7L, 6XMG, 6W5C, 5XWP

I am happy to conclude my trilogy on Cas9 specificity with our new preprint from the @MartinJinek lab! We solved a staggering number (15!) of crystal structures of Cas9 bound to bona fide off-targets to investigate the nature of mismatch tolerance.

biorxiv.org/content/10.110… We observe that mismatch tolerance is primarily facilitated by the formation of non-canonical base pairs within the heteroduplex. This effect is dependent on the type of mismatch, the surrounding nucleotides, and its position within the duplex.