The Tortured Proteins Department

NIH Strategic Plan Comments (Due 5/26)Preprint: Cooling fast and slow: Characterising the effects of vitrification in cryo-EM and the subsequent recovery of equilibrium populationscryoAgent: An agentic workflow for robust and adaptive end-to-end cryo-EM image processingYou need to make AI guidelines for your labWe’re Training Scientists for a World That No Longer Exists

diffUSE ProjectApril Fools Blog NIH News:Funding CurveDrug Monkey 2025 Grant ReportHow the 2025 NIH grant terminations varied by researchers’ demographic groupsPreprints: Intrinsic dataset features drive mutational effect prediction by protein language modelsRibosome Molecular Aging Shapes Translation DynamicsAI Grad Student:Why I may ‘hire’ AI instead of a graduate studentVibe physics: The AI grad student

Topics:OlympicsNIH Bureaucracy - Grants & LeadershipsPreprints12 episodes of TTPD! Claude Code & Slack AppsSan Francisco HalfPreprints: Bidirectional allosteric ligand regulation in a central glycolytic enzyme Large-scale exploration of protein space by automated NMR

Preprints:Improving Cryo-EM Optimization Robustness with an Optimal Transport Loss Function for Noisy ImagesProtein folding success depends on the direction and speed of polypeptide chain appearanceJeremy Reiter's gene list

Year in Review & 2026 PredictionsPreprints:Rewriting protein alphabets with language modelsFine-tuning protein language models on human spatial constraint yields state-of-the-art variant effect predictionPrachee Avasthi Blog Post:How to Not Make a Scientific Journal by Accident

Topics:Government Shutdown/ReopeningTravels The impact of Jane RichardsonAI Peer Review toolsPreprint 1: Hit or Miss: Understanding Emergence and Absence of Homo-oligomeric Contacts in Protein Language ModelsThe Drain of Scientific Publishing Big experiments are only big if they can fail

Topics:Compact for Academic Excellence in Higher EducationGovernment ShutdownHHMI's new open science policiesShrinking PhD poolsThe Nobel PrizesThe BearTLOS ReactionsPreprint: Experiment-guided AlphaFold3 resolves accurate protein ensembles

Latest News:-H1B changes & chaos-Who determines what gets into Pubmed (Literature Selection Technical Review Committee) Preprints:Generative design of novel bacteriophages with genome language modelsImproved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching High-resolution ab initio reconstruction enables cryo-EM structure determination of small particles (See great biorxiv comment on the paper!)

We chatted about the recent meetings, latest news, open science, social media, and, of course, the recent engagement.Preprints:Aromatic Ring Flips Reveal Reshaping of Protein Dynamics in Crystals and ComplexesComputational design of conformation-biasing mutations to alter protein functionsWhy do we still publish in scientific journals? - Pedro Beltrao's blogThe diffUSE ProjectOpenADMET

We chatted about the latest news, including the new NIH open access policy, trends observed with scientists using LLMs, & the Montpelier Mile race. "The new Administration began weaponizing what should not be weaponized - the health of all Americans...creating chaos and promoting an...unreasoned agenda of blacklisting certain topics, that...has absolutely nothing to do with the promotion of science." - Judge William Young (reported by Max Kozlov, Nature News) An Evaluation of Biomolecular Energetics Learned by AlphaFoldProduct-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity

- News round-up- Conformational Ensembles Conference- Preprints discussed: Multiscale guidance of AlphaFold3 with heterogeneous cryo-EM data (https://www.arxiv.org/abs/2506.04490)Boltz-2 Towards Accurate and EfficientBinding Affinity Prediction (https://jeremywohlwend.com/assets/boltz2.pdf) - Guiding vibe coding for science-Dipsea & Montpelier Mile

The preprints discussed in this episode. Structures of protein folding intermediates on the ribosome:https://www.biorxiv.org/content/10.1101/2025.04.07.647236v1.full.pdfAF2χ: Predicting protein side-chain rotamer distributions with AlphaFold2:https://www.biorxiv.org/content/10.1101/2025.04.16.649219v1.full.pdf

We chatted about the continued chaos of science infrastructure and dived into some cool science from recent meetings Jaime and Stephanie attended. We introduce two new segments: preprints and how to do science. The pre-prints discussed in this episode: Counting particles could give wrong probabilities in Cryo-Electron Microscopy- https://www.biorxiv.org/content/10.1101/2025.03.27.644168v1Enthalpy-entropy trade-offs in the evolution of ligand specificity in a superfamily of transcription factors- https://www.biorxiv.org/content/10.1101/2025.03.23.644840v1?rss=1Conserved energetic changes drive function in an ancient protein fold- https://www.biorxiv.org/content/10.1101/2025.04.02.646877v1

Episode 1. We discuss the declining support of science in the US and how it may impact the future of graduate science education. Recorded- 3/14/2025