Savvas Savvides Lab

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Improved protein binder design using beta-pairing targeted RFdiffusion 🚀 New preprint from David Baker!🚀 • A breakthrough in protein binder design: this study uses RFdiffusion conditioned to generate binders that form precise beta-strand pairings with polar protein targets, yielding binders with superior affinity and specificity. • The approach focuses on polar regions of target proteins, especially edge beta-strands, addressing the challenge of complementing hydrogen bond donors and acceptors that are otherwise exposed to water. • Designed binders achieved affinities ranging from 76 pM to mid-nanomolar, targeting therapeutically relevant proteins like KIT, PDGFRɑ, and ALK-2, with no significant off-target binding. • A co-crystal structure of a binder in complex with the KIT receptor confirms the computational accuracy of this new design method, showcasing near-perfect matching of the design model and real-world interactions. • This beta-strand focused method not only enhances the range of RFdiffusion’s capabilities but also expands the potential for developing new therapeutic binders targeting polar protein surfaces, such as those in cancer-related pathways. • The new design approach surpasses traditional methods, particularly in targeting polar regions and edge beta-strands in proteins like ALK-2, ALK-3, and PDGFRɑ, where previous techniques failed to generate effective binders. • The study demonstrates that beta-strand pairing conditioned designs have higher thermal stability and are more specific in binding compared to earlier models, making them valuable for therapeutic applications like receptor targeting and drug delivery. @UWproteindesign @SavvidesLab @StevenMBanik @TimothyPJenkins @Green_Ahn @MelBenard86 @kf_verstraete @SusanaVazTor @_JosephWatson @martin_toul 📜Paper: doi.org/10.1101/2024.1…

Read the preprint bit.ly/3QpiUk1 describing a milestone in our de novo antibody design efforts. Our pipeline can now design high-affinity and stable antibodies in a single round! Fantastic collaboration with @lab_serrano @SavvidesLab & Maarten Dewilde @KU_Leuven

Happy to share the #preprint on #denovo #antibody design in a single round yielding stable Abs with high affinity: lnkd.in/ew5ATYHy Grateful to be part of great collaboration efforts betwen @VIB_Switch_Lab @KU_Leuven @CRGenomica @InflamResCen @VIBLifeSciences @ugent

biorxiv.org/content/10.110… A prodigious effort and interdisciplinary collaborative work by @VIB_Switch_Lab at @VIBLifeSciences @KU_Leuven , @lab_serrano at @CRGenomica, @SavvidesLab at @VIBLifeSciences @InflamResCen @ugent, and Maarten Dewilde Lab @KU_Leuven

Training the next generations of scientists in experimental structural biology. We are grateful to @synchroSOLEIL and @Proxima2A for hosting our Master program in Biochemistry-Biotechnology @ugent for a practical workshop on X-ray crystallography.

@MSCActions @GoossensLabVIB Bart Ghesquière @jennyrussinova @frbre @lab_marine @RaesLab @jeroenraes @FarrowLab @AgostinisLab @Verstreken_Lab @VanderhaeghenP2 @MancusoRenzo @FendtLab @SavvidesLab @steinaerts @martin_toul @AvilienDard @yongming_luo Kresimir Sola @M4riekeHoekstra Célia Lentini

Delighted to share our work in @NatureSMB on #structures of IL-12/23 cytokine complexes involving the complete extracellular domains of IL-12 family receptors, jointly celebrating 30 years of IL-12 receptor #immunology and @NatureSMB nature.com/articles/s4159…

HAPPY 30th BIRTHDAY TO US🎂 First issue of NSMB came out in January 1994. Come celebrate with us 30 years of changes and progress in structural and molecular biology nature.com/nsmb/volumes/3… We are continuing celebrations throughout the year with more content, so stay tuned!

Continuing the brainstorming session at a #Brussels institution #MortSubite

We just had a very exciting, educational, and interactive symposium on #AI in #StructuralBiology hosted by @VSC_HPC and @FWOVlaanderen…Prediction cannot happen without experiments! #AlphaFold #StructurePrediction #XrayCrystallograpy #CryoEM

Ex vivo X-ray crystallography meets Immunology inside and outside the box in our latest collaborative work with @bart_lambrecht and colleagues at the @InflamResCen and @ugent doi.org/10.7554/eLife.…

Great start to an inspirational #cytokines2023 at the foot of the Acropolis @CytokineSociety

We are heading with a team of seven to Athens, Greece for a very exciting #cytokines2023

@puxano Congratulations to the innovators at Puxano. We are delighted to be collaborating with them.

Big thanks to @synchroSOLEIL & @Proxima2A for giving our @ugent students a memorable visit and an on-site view into both theory & practice in #proteincrystallography! #structuralbiology @LM_UGent

@Proxima2A Many thanks for hosting us and giving students a great learning experience!

PROXIMA 2 hosted students and tutors from the University of Ghent for practicals, tutorials and lectures covering all the steps in X-ray crystallography - crystallisation, harvesting, data collection, structure determination and Savvas Savvides' most famous crystallography quiz!

Check out the latest issue of @NatureSMB featuring Tsirigotaki et al. nature.com/articles/s4159… on the Leptin-mediated receptor complex as a cover story and additional coverage via a News & Views article nature.com/articles/s4159…

Given ISOLDE is a model-fitting tool, it was about time I gave it a way to, you know, actually validate the fit of a model to a map. As such, in consultation with Greg Pintille and Tom Goddard I've implemented the Q-Score algorithm (nature.com/articles/s4159…) in ChimeraX. (1/2)

We're thrilled to share that @Savvideslab's mechanistic and #structural studies on newly described #trimerization of #Leptin receptor has been published @NatureSMB today! Many congrats to everyone contributing to this work! @VIBlifesciences nature.com/articles/s4159…