Reading · This Week In Cheminformatics

This paper from CCDC asks if your docking tool needs a binding site as input, and you don’t have one, is cavity prediction actually good enough to bridge that gap? They ran four cavity predictors (PUResNet-2.0, LVPocket, CAVIAR, Fpocket) on 486 curated protein-ligand structures and fed the best predicted cavity into GOLD, using four different ways of translating a cavity into a binding site definition (atom-vicinity vs. residue-vicinity, at 10 and 12 Å). Fpocket and CAVIAR come out ahead on cavity centroid accuracy (means of 3.5 and 4.2 Å vs. 6.6-6.9 Å for LVPocket/PUResNet-2.0), and centroid-based cavity definitions consistently beat residue-based ones for GOLD, likely because residue expansion drags in false-positive atoms that GOLD’s scoring can reward. The more interesting result is correlation between cavity accuracy and final pose accuracy drops to 0.49 when restricted to the two best cavity methods, meaning close-enough cavities don’t reliably translate to correct poses, and conversely some docking runs succeeded even with cavity centroids >9 Å off. They also benchmark against DiffDock and Boltz-1 blind docking, where GOLD+Fpocket/CAVIAR wins on mean distance but DiffDock has a lower median with heavier-tailed outliers (quite not the usual “AI blind docking dominates” narrative you see elsewhere). Good read !

Kurczab’s group keeps pushing the “spectra as descriptors” line, and this one tests the question that actually matters: is NMR redundant if one uses ECFP4, or does it add something ? They built SpectraPRINTS which is concatenation of binned predicted ¹H/¹³C shifts (400-dim, HOSE-code/nmrshiftdb2-derived) with ECFP4. They ran the identical CNN regression pipeline across logP, logS, logD at three pH values, and both macroscopic pKa endpoints, so any difference in RMSE is due to representation and not architecture. They observed that lipophilicity/solubility endpoints get consistent gains (16–39% RMSE reduction, largest at logD pH 10.5), while pKa shows no systematic improvement which interestingly they attribute to macroscopic pKa collapsing multiple protonation microstates/tautomers into one number, which makes sense. They also shipped it as a live webapp (link here: NMR-AI).

Docking benchmarks have long leaned on the Astex diverse set and its ~2 Å RMSD success criterion, but this paper points out that criterion quietly assumes there’s one right answer to find. Kubincová et al. instead curate 60 PDB structures with alternate locations for the same ligand. These are crystallographically resolved binding-mode pairs, split into ring flips, ring puckers, and other rearrangements. They ask four templated docking protocols (RDKit/smina, rDock, PLANTS, AutoDock-GPU) to recover the non-input pose when given the other as a starting point. Success drops to 30–50% after pose selection, versus 70–90% on Astex (!!) even though the docking is templated and should have been easier. Worth reading if you rely on docking to generate starting poses for RBFE. The paper argues (and I think reasonably) that the 2 Å criterion from virtual-screening benchmarks doesn’t transfer to the pose-curation use case, where getting the wrong binding mode can cost you several kcal/mol downstream.

I made an app for Garmin watches with gentle reminders to be present in the moment, might be of interest to some : https://github.com/Manas02/HereAndNow

Miss Sentient@0xsachi

He didn’t get the h1b lottery and got kicked out

signüll @signulll

kimi’s founder & ceo got his phd at cmu. why didn’t he stay in america?!

7:34 AM · Jul 17, 2026 · 549K Views

166 Replies · 141 Reposts · 5.32K Likes

patagucci perf papi@kenwheeler

“yeah no i’m really excited to implement agentic solutions”

12:05 AM · Jul 17, 2026 · 27.2K Views

10 Replies · 24 Reposts · 1.06K Likes

AJ Stuyvenberg@astuyve

Watching everyone open their AWS billing console this morning

12:41 PM · Jul 17, 2026 · 16.1K Views

8 Replies · 17 Reposts · 729 Likes

IroncladDev@IroncladDev

just finished learning the kubernetes course from @bootdotdev

1:56 AM · Jul 17, 2026 · 15K Views

17 Replies · 37 Reposts · 701 Likes

delyth@StasioEnjoyer

Yo who the fuck is Michael and why is he in my kernel

3:58 PM · Jul 16, 2026 · 71.2K Views

41 Replies · 64 Reposts · 1.87K Likes

dandelion georgism 🔰🏗@DolphinMossad

1995: oh cool you can buy books online now 2026: the company that owns Whole Foods and Lord of the Rings is experiencing setbacks with its space program

Jon Erlichman @JonErlichman

On this day in 1995: Amazon launched.

6:00 PM · Jul 17, 2026 · 1.03M Views

70 Replies · 3.57K Reposts · 49.1K Likes

Drew Young@DrewYoungRadio

This kid is a legend 😂 can we please make this a gif #MLS #STLCITYSC #ALLFORCITY

Ben Pfeiffer @bpfeiff24

@DrewYoungRadio If someone makes a gif of the clip they showed at the game. *chef’s kiss* Up there with this beaut:

4:45 AM · Jul 17, 2026 · 35.8M Views

557 Replies · 20.7K Reposts · 337K Likes

The Cinéprism@TheCineprism

Rare asthetics: IMAX front row seats

6:35 AM · Jul 17, 2026 · 2.01M Views

176 Replies · 3.13K Reposts · 68.4K Likes

Ash Jogalekar@curiouswavefn

German physical chemist Angela Merkel was born #OTD 1954. Here's a paper from her early research, a computational study of an organic reaction, published in J. Amer. Chem. Soc. in 1988. Merkel also served as chancellor of Germany from 2005-2021.

6:24 PM · Jul 17, 2026 · 1.89K Views

1 Reply · 5 Reposts · 53 Likes

Bharath@Bharath_uwu

I just saw $1.5 trillion on my AWS bill and my soul left my body

AWS Support @AWSSupport

📣 Service Update: AWS Billing Console We are investigating issues with Cost Explorer reflecting inaccurate estimated billing data. 📊 Track status: https://t.co/6qSnkuEzc4 #AWS #AWSSupport

9:04 AM · Jul 17, 2026 · 2.3M Views

488 Replies · 1.16K Reposts · 25.2K Likes

Sen@senbuilds

Trillion dollar company btw

8:46 AM · Jul 17, 2026 · 411K Views

301 Replies · 418 Reposts · 12.9K Likes

roxy@hendrixnroses

9:24 PM · Jul 16, 2026 · 2.81M Views

184 Replies · 19K Reposts · 233K Likes

Evan Applegate@youwillmakemaps

3:48 PM · Jun 8, 2025 · 80.5K Views

8 Replies · 21 Reposts · 301 Likes

Christopher Akiki@christopher

O'Reilly animals sorted by orientation using PCA.

Christopher Akiki @christopher

Image quilt of all @OReillyMedia book covers sorted by color. https://t.co/GJrb2SUlK8

6:57 PM · Jul 16, 2026 · 194K Views

14 Replies · 193 Reposts · 2.45K Likes

Donald Mitchell@DonaldPMitchell

IBM transistor. Conductors 15 atoms thick.

3:31 AM · Jul 17, 2026 · 2.96M Views

96 Replies · 597 Reposts · 7.78K Likes

Dmitrii Kovanikov@ChShersh

Modern C++ is basically Python with UB and a 900-page standard. The following is valid C++ (zero macros)

4:41 AM · Jul 16, 2026 · 52.6K Views

57 Replies · 32 Reposts · 930 Likes

ThePrimeagen@ThePrimeagen

Discovering what we already knew from first principals

Kr$na @krishdotdev

The new development cycle in one image.

10:17 PM · Jul 16, 2026 · 166K Views

74 Replies · 169 Reposts · 5.41K Likes

Lawrence Jang@JangLawrenceK

my biggest fantasy is becoming a reality

Andy Fang @andyfang

Today we're opening up the DoorDash CLI in limited beta. `dd-cli` lets you order DoorDash directly from your agent: search stores, find the best deals, check out, and more. Early access for US/Canadian macOS developers by waitlist. Excited to see what folks build!

7:02 AM · Jul 16, 2026 · 850K Views

22 Replies · 268 Reposts · 9.74K Likes

Havoc@Havoc_Six

11:11 PM · Jul 15, 2026 · 718K Views

61 Replies · 4.31K Reposts · 105K Likes

Wellu@Wellutwt

Watching nolan masterpiece #TheOdyssey

6:22 AM · Jul 16, 2026 · 4.94M Views

1.37K Replies · 13.7K Reposts · 260K Likes

Alex@Alex_FF

Tell Codex to open Microsoft Paint and try to draw you

2:00 PM · Jul 15, 2026 · 1.09M Views

226 Replies · 179 Reposts · 6.5K Likes

Tzo@Go__5356

5:45 AM · Jul 15, 2026 · 79.9K Views

16 Replies · 314 Reposts · 3.61K Likes

Michael Baym@baym

the people yearn for grad school

Oscar Hong @oscrhong

a “gym for your mind” will be the next breakout product / movement everyone reaches this conclusion after their ai honeymoon phase. yes you got the result you wanted—work done, app built, revenues up—but not the *feeling* of doing great work aka mastery idk what shape this

3:25 AM · Jul 16, 2026 · 20.8K Views

7 Replies · 30 Reposts · 507 Likes

techbimbo@jameygannon

irony is you couldn't recreate this now if you tried

Riley Hennigh @rileycx

honestly the will smith spaghetti was peak ai

8:05 PM · Jul 14, 2026 · 14.2M Views

510 Replies · 6.25K Reposts · 200K Likes

ThePrimeagen@ThePrimeagen

@camiinthisthang jokes on you, i had no value before chatgpt 3.5 came out

4:35 PM · Jul 6, 2026 · 5.79K Views

7 Replies · 154 Likes

no context memes@nocontextmemes

2:55 PM · Jul 13, 2026 · 1.38M Views

122 Replies · 4.61K Reposts · 127K Likes

Signing off one last time from PT ; )
Muito Obrigado,
Manas

This Week In Cheminformatics: Issue #030

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