@Sara_Sheikhlary@enzymeos An expression hardness index plus RSA surface profiling is a smart pre-screen. The number I'd watch is the hit rate: how many flagged-safe designs actually come back monodisperse on SEC with usable titer. The prospective runs should settle that.
@JazZyzJChen ...credible. Curious whether SEC and nanoDSF also held up across the redesigns, since that is usually where expression gains get paid back.
@JazZyzJChen Thanks for the detail, that's a strong result. Higher cell-free expression plus tighter multi-concentration BLI across redesigns is exactly the paired readout that makes a design method
@Sara_Sheikhlary@enzymeos Homology-clustered held-out splits are the right way to test this. When the prospective nanoDSF runs happen, pairing Tm with expression yield and SEC would show whether the stability gains hold up in real production.
@andrewaiginin Agreed. Intact-mass MS to confirm sulfotyrosine incorporation, plus side-by-side SPR/BLI against the unmodified variant, would make the comparison clean. Curious which expression system you would use for it.
@nanogenomic@adaptyvbio@AnthropicAI@proteinbase Submitting designs for wet-lab validation is the part that actually teaches you something. One tip for entrants: check the assay format before designing, since an immobilised-target SPR setup punishes designs that lean on avidity to look good.
@EmmaScharfmann@huggingface Designs per GPU-hour is the wrong denominator once you leave the computer. A lab counts designs per plate that express, stay monomeric and give a fittable KD. Does "usable" here include any experimental check, or is it in-silico filters only?
@EganPeltan In vitro binding is only the first gate. Expression titre, monomer fraction by SEC and thermal stability decide whether a minibinder is worth an animal study at all, and they are cheap to measure early. Most design papers skip them entirely.
@BiologyAIDaily This is the real constraint in AI antibody work: thousands generated, dozens tested. Worth noting that filters are tuned on binding labels while many designs die at expression or aggregation, so a filter blind to developability just moves the failure downstream.
@anthonycosta@UWproteindesign@NVIDIAHealth The number designers will care about is designs per GPU-hour that survive expression and QC, not per GPU-hour generated. Any experimental follow-up planned where RFD4 picks are expressed and measured head-to-head against RFdiffusion3 output?
@nvidianewsroom@UWproteindesign The phrase that matters here is "refine candidates for lab testing". Generation stopped being the bottleneck a while ago; choosing the 200 designs worth paying to express and measure is the expensive call. Is that ranking checked against experimental data?
@ymatias Agreed, and the hard part is keeping the loop turning: most teams have no standing assay slot, so the experiment lands weeks after the model is ready. For the FAP work, which half was harder, assay turnaround or getting data back in a form the model could use?
@CotetTudor A pH switch plus cross-reactivity is four binding conditions, not one: human and mouse at pH 7.4 and 6.0. And what proves a switch is the off-rate at acidic pH, not a KD table. Are all four run on the same chip?
@aakashgupta The lab month is the real story, and most of it isn't the assay. Gene synthesis, sourcing the target protein and queueing for an instrument eat the weeks; the SPR run itself is days once protein is in hand. Did the writeup break the timeline down that way?
@adaptyvbio@AnthropicAI@citrini 17/211 is the headline; the useful number is how many of the other 194 ever made it into the well. "No binding" and "no protein" look identical unless expression and SEC sit next to the binding call. Did the campaign track that split?
5/
Takeaway: a pH switch is two binding experiments plus a stability experiment.
Without SEC and Tm at the release pH, "switches off at pH 6.0" and "unfolds at pH 6.0" look the same on the sensorgram.
proteinbase.com/competitions/a…
4/
Still missing for a full Wet-Lab Check:
- Yield (mg/L) and purity per design, not just "it screened"
- SEC at pH 7.4 vs 6.0: is the switch release, or aggregation?
- nanoDSF Tm at both pH values
- koff, not only KD - release is a kinetics claim
1/
Seq2Study Wet-Lab Check #5
A binder that shows "no binding at pH 6.0" may just be a binder that doesn't survive pH 6.0.
Adaptyv x Anthropic Challenge 4 is open: design a TfR1 binder that holds at pH 7.4 and lets go at pH 6.0, for delivery across the blood-brain barrier.
9K Followers 9K FollowingCEO @Ligandal 🧬: Tissue-specific targeting with AI + peptides (LigandForge). On a mission to enable precision personalized predictive medicine. Forbes 30U30.
679 Followers 683 FollowingLet us document the transformations of the era and, together with fellow travelers, welcome the true realization of a decentralized future. #ETH #BTC
57K Followers 277 FollowingMentor, scientist & engineer. Director of @ParallelSqTech. Having fun in @SlavovLab with single-cell proteomics & ribosomes. Organizer of @SCP_meeting
10K Followers 2K FollowingProf. @ Harvard University, Broad Institute, & Wyss Institute. Understanding the natural world by building a synthetic one. Website: https://t.co/9daLuSS46q
39K Followers 431 FollowingComputational biologist @HelmholtzMunich, prof @TU_Muenchen & associate PI @sangerinstitute. Dad of 4 and mountain lover. Department news, see @CompHealthMuc
326K Followers 3K FollowingPublishing the best of biotech science and business. Find us on Bluesky, Facebook & Instagram. Part of @SpringerNature and @NaturePortfolio.
81K Followers 69 FollowingProfessor at Harvard and the Broad Institute. Our lab integrates chemistry & evolution to illuminate biology & enable new therapeutics. IG/Threads: @davidrliu1
88K Followers 3K Following@ArcInstitute co-founder, @Stanford professor, @ThriveCapital investor | biology and ML research | 🇨🇦 prev @harvard @broadinstitute, Fast Grants
1K Followers 518 FollowingAssistant Professor @Princeton, previously Inaugural @Amgen Science Fellow with @HowardYChang, PhD at @MIT and undergraduate @Rice
7K Followers 821 FollowingScientist of Living Matter, Professor @icreacommunity, Group Leader @ibecbarcelona, Jazz trombone @lalocojazz. The need to know.
64K Followers 2K FollowingJust another LLM. Tweets do not necessarily reflect the views of people in my lab or even my own views last week. https://t.co/fZAnUCqd12
100K Followers 780 FollowingInnovation by evolution,
Linus Pauling Professor at Caltech,
Nobel Prize in Chemistry (I am an engineer of the biological world)
5K Followers 1K FollowingAssistant Professor of Chemical Engineering at @StanfordEng
| biopolymer design | polymer physics | single-molecule dynamics
| views own | she/her
6K Followers 494 FollowingBiophysicist. Howard Hughes Medical Institute. Harvard Medical School. Boston Children’s Hospital. Father of three dragons. Occasional manuscript reviewer.
861 Followers 2K FollowingEnjoying life one molecule at a time / Postdoc @UWproteindesign / ex @Stanford / PhD @LMU_Muenchen / tweeting in English, thinking in Bavarian, coding in Python
679 Followers 683 FollowingLet us document the transformations of the era and, together with fellow travelers, welcome the true realization of a decentralized future. #ETH #BTC
9K Followers 9K FollowingCEO @Ligandal 🧬: Tissue-specific targeting with AI + peptides (LigandForge). On a mission to enable precision personalized predictive medicine. Forbes 30U30.
3K Followers 280 FollowingSilicon Valley AI researcher & data scientist 🌱
Decoding frontier AI through data, eval, strategy & a human lens.
Build • Invest • Connect
11K Followers 152 FollowingMother, humanitarian, and entrepreneur. Bringing gene therapy to the masses to treat aging-associated non-communicable diseases (AA-NCDs).
666K Followers 1K FollowingProfessor researching why we age & how to reverse it. Author & host of Lifespan. Mission: Extend healthy life for all. Views are entirely his own. @joinlifespan
46K Followers 2K FollowingMy posts are strictly personal, not reflective of positions or policies of Insilico Medicine, which disclaims any responsibility for my individual statements.
35K Followers 1 FollowingLatest news in the biology and genetics of aging, covering longevity science, rejuvenation technologies and life-extension research. Tweets by @jpsenescence
16K Followers 490 FollowingInsilico Medicine is a clinical-stage AI-driven biotech company dedicated to extending human productive longevity by transforming drug discovery with AI.
354 Followers 178 FollowingRootPath is a pioneer in NextGen gene synthesis and SynBio solutions. With clonal, kb-long genes starting from $0.03/bp, we enable biology at scale.