iiinova — where your digital self keeps evolving

Will Fondrie @willfondrie.com · 30/07/2026

(11/13) I guess what I'm trying to say is: Welcome to the structure-free future of drug discovery.

Mean Girls Meme: "Get in loser" "We're doing structure-fress drug discovery"

Will Fondrie @willfondrie.com · 30/07/2026

(10/13) My favorite story is about the recent STAT6 inhibitors disclosed by Pfizer. Ptarmigan-1 is not only able to enrich for these in a screening scenario, but also localizes them to a shallow groove on the SH2 domain.

Ptarmigan-1 finds and localizes STAT6 inhibitors.

130

Will Fondrie @willfondrie.com · 30/07/2026

(9/13) Now the targets we actually built this for: 👉 intrinsically disordered: Boltz-2 goes near random, Ptarmigan-1 still enriches for active ligands 👉 cryptic pockets on CryptoBench: we beat P2Rank despite this being zero-shot, never trained to find pockets.

130

Will Fondrie @willfondrie.com · 30/07/2026

(8/13) Localization is where it gets fun. We score every residue and get a binding site map from sequence alone: 👉 top residue within 5 Å of the ligand for 92% of drug-like PoseBusters complexes 👉 engaged cysteine in the top 1% for 8 of 9 COValid targets, held-out ones included

Ptarmigan-1 can localize compounds to where they bind.

130

Will Fondrie @willfondrie.com · 30/07/2026

(6/13) A screen with Ptarmigan-1 is just a nearest-neighbor lookup instead of a simulation. This clocks in at 10 ms per compound - ~5,000x faster than when we ran Boltz-2 on the same hardware. All 20,431 human proteins against a 3.4B compound library: 20 H100-hours.

A figure showing how fast Ptarmigan-1 is.

120

Will Fondrie @willfondrie.com · 30/07/2026

(5/13) Protein-level labels from bioactivity can be used. Residue-level labels from chemoproteomics data can be used. We can even extract residue-level labels from the structures in the PDB. Key to it all: our massive swath of internal data on the disordered proteins of the regulome.

120

Will Fondrie @willfondrie.com · 30/07/2026

(3/13) So we skipped the structure. Ptarmigan-1 embeds every residue of a protein and every compound into one shared latent space, using fine-tuned foundation models for sequence and chemistry. The residue-level resolution is the real innovation here. Engagement is just cosine similarity. 🤖

A schematic of how Ptarmigan-1 co-embeds proteins and compounds.

120

Will Fondrie @willfondrie.com · 03/06/2026

#ASMS2026 coffee pilgrimage day 4: Torque Coffee. I had a nice cortado with their lighter espresso, Yellow Diamond (yes, they have two options!) This one is a bit further out in North Park, but a nice trek for some good coffee. Thanks for the rec @michaellazear.bsky.social!

A nice cortado on a green plate with a bubbly water beside.

040

Will Fondrie @willfondrie.com · 02/06/2026

#ASMS2026 coffee pilgrimage day 3: Goldchild coffee. It's a bit of a hike downtown, but 100% worth it. This one is the best I've tried so far. www.goldchildcoffee.com

110

Will Fondrie @willfondrie.com · 22/02/2026

Saw a post about GPU depreciation and I could hardly believe what second-hand H100s were selling for. The GPU market is wild.

030

Will Fondrie @willfondrie.com · 18/12/2025

Ha. Good to know I still get to code a bit 😀 git-wrapped.com

110

Will Fondrie @willfondrie.com · 27/08/2025

It was nice to get away to Mt Rainier 🏔️ for a long weekend camping trip. We even got to see some marmots!

Crossing a river on the trail at Mt Rainier

060

Will Fondrie @willfondrie.com · 08/08/2025

Definitely PhD level. No question 👏 But seriously, I thought other folks were joking 🙃

100

Will Fondrie @willfondrie.com · 04/07/2025

Even with everything going on, happy Indepenence Day to my friend in the US. Here is a version of “Battle Hymn of the Republic” that I’ve been working on. 🪕 I’ll eventually learn to sing, but today is not that day 🙃

050

Will Fondrie @willfondrie.com · 05/06/2025

Stop by poster ThP 289 to… calmly discuss… metadata collection and management with Anastasiya 👏 #ASMS2025

2214

Will Fondrie @willfondrie.com · 05/06/2025

It was a lot of fun participating in the Biomarker workshop panel at #ASMS2025. Thank you to all of you who were there! Also, they got some pictures:

1213

Will Fondrie @willfondrie.com · 01/06/2025

That’s a wrap on our #ML for #MassSpec short course at #ASMS2025 🎉 Thanks to all of the participants who made it a joy to teach 👏

0234

Will Fondrie @willfondrie.com · 01/06/2025

Fueling up with a cortado at Ceremony again this morning Come see my poster #ASMS2025 on Tuesday about our recommender system method for predicting the retention times od undetected peptides… called Cortado 😉 #ASMSBmoreEats

010

Will Fondrie @willfondrie.com · 27/05/2025

The sad news is that my hiking boots for the last 12 years finally deteriorated. So many adventures in them! The AT, Harpers Ferry, Chincoteague, 3 ft of snow in Baltimore, MN trails, Rainier, all kinds of trails in WA… You will be missed 🫡

040

Will Fondrie @willfondrie.com · 27/05/2025

First camping trip of the season done and dusted 🏕️ It was great to disconnect for a few days and I’m looking forward to the others we have planned this summer!

080

Will Fondrie @willfondrie.com · 14/05/2025

Quote skeet with a picture of the airplane you'll accept as a bribe

020

Will Fondrie @willfondrie.com · 29/04/2025

@jspaezp.bsky.social is talking about #AI in #Proteomics tomorrow as part of a webinar put on by @us-hupo.org and @abrf.bsky.social. Join in and hear about how ML and AI are integrating into all aspects of the proteomics workflow! 🤖 Register here 👇 us02web.zoom.us/webinar/regi...

A flyer for the event, happening at 9am PST

000

Will Fondrie @willfondrie.com · 25/02/2025

Quote post with a picture you took in a National Park Mt Rainier National Park last summer 🏔️

030

Will Fondrie @willfondrie.com · 06/02/2025

Explored another kind of peak yesterday @eubic-ms.org 🏔️ #massspec

2292

Will Fondrie @willfondrie.com · 09/01/2025

I had fun writing a bit about #AI for #DrugDiscovery with Milad and Megan 🤖 Two thoughts: 👉 It's all about the data. Co's that have the best, proprietary data to power their models will win the day. 👉 A tightly coupled wet and dry lab shorten the active learning feedback loop. (1/3) 🧵

The active learning feedback loop, where constant experimental feedback lead to improvements across every step of the drug development cycle.

160

Will Fondrie @willfondrie.com · 04/01/2025

We got outside today and it was a refreshing break from the final grant writing push this week 😊

070

Will Fondrie @willfondrie.com · 17/12/2024

The kids wanted me to watercolor with them this weekend. They asked me to paint a robot 🤖 I think I nailed it 😉 …and ended up with a winning white elephant gift for someone this week? 😂

A very amateur watercolor of a mountain landscape with a familiar pair of droids looking at a tree.

040

Will Fondrie @willfondrie.com · 26/11/2024

My first wetlab experiment in years was a success! I taught the my budding scientists about chromatography this morning. We separated colors in markers using coffee filters 🧑‍🔬 They’re well on their way to joining #TeamMassSpec 😉