RT @CRGenomica: Introducing Human Domainome v1, the largest and most comprehensive library of human protein variants to date, which maps th….

RT @MarcdeManuel: 📣 Two ERC-funded positions are available in the lab! If you’re interested in exploring the mechanisms underlying mutation….

RT @BenLehner: The genetic architecture of protein stability.by @aj4re @ainamartiaranda @cristonah @ToniBeltran13 @JoernSchmiedel. https:/….

RT @BenLehner: Excited to share @AlbertIltirda's randomisation of protein cores at scale: Genetics, energetics and allostery during a billi….

RT @hackettlab: How do chromatin modifications quantitatively impact gene expression?. How do sequence variants or combinatorial marks infl….

RT @hackettlab: The gut microbiome influences metabolites, hormones and immune function. Perturbing gut microbiota therefore impacts homeos….

RT @DavidSalesaD:

RT @BenLehner: @ToniBeltran13 @CRGenomica @sangerinstitute That's the Src kinase domain alone. Here's the allosteric map of the kinase dom….

RT @BenLehner: Thread by @ToniBeltran13 about the Src kinase allosteric map. And here is one view of the map. @CRGenomica @sangerinstitute….

I'm super grateful to have had the support of all the Lehner lab members, and of course of @aj4re and @BenLehner. We are super excited to expand this approach to other kinases and enzymes next! 🧬🧑‍🔬💻.

This complete allosteric map also allows us to take an unbiased look at the surface of the kinase. Many surface pockets are enriched in inactivating allosteric mutations, and we think these might be interesting sites to target with drugs in the future! 💊.

We recapitulate previous molecular dynamics work on the Src allosteric network, and we expand the set of allosteric residues to many more all over the kinase domain. Look at this cool exponential decay of mutational effects on activity with distance to the active site!

We measured the effects of mutations on both protein abundance and activity and used energy models (shout out to @aj4re!) to isolate the specific effects of mutations on activity across the entire kinase domain. This allows us to study long-range allosteric effects!.

We decided to apply this method to protein kinases as most inhibitors target kinase active sites and have poor specificity. 💊 But how can we find other sites in a kinase that might be good targets for modulation of activity? 🤔.

I’m super happy to finally share what I have been up to the last few years at the @BenLehner lab in Barcelona! We made lots of double mutants on the kinase domain of Src to study allosteric communication.

RT @magdatopolska1: Excited to share a new, MUCH IMPROVED version of our deep indel mutagenesis (DIM) manuscript:.S….

RT @taraneh_z: Very happy to share what I've been working on in Barcelona with @BenLehner ! We made many (>400k) mutations in a disordered….

RT @BenLehner: Excited to share @taraneh_z's preprint: A complete map of specificity encoding for a partially fuzzy protein interaction ht….

RT @magdatopolska1: Excited to finally share some of my PhD work on quantifying the effects of indel mutations on protein stability and fun….

RT @BenLehner: New preprint from the lab:.Deep indel mutagenesis reveals the impact of insertions and deletions on protein stability and fu….