The Savvides lab @InflamResCen and @ugent employs #IntegrativeStructuralBiology to study proteins pivotal to inflammation, immunity and cancersavvideslab.sites.vib.be/en#/ IRC-VIB, Ghent, BelgiumJoined March 2023
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
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.
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!
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!
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)
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