Advertise on podcast: The Tortured Proteins Department

We talk about ANOTHER big travel month, federal fights over science funding, preprints, and the intersection of AI and scientific discoveries News Links: Inside the US military's plan to tap huge sums from the NIH New lawsuit accuses Trump administration of blocking NIH grants as form of censorship Trump asked budget chief to draft order bringing health research funding under his control Preprints: De novo Rubisco design with protein language modelsOptimizing the connectivity of protein conformations to untangle ensemble refinement Reimagining research papers as interactive and reliable AI agents Did Anthropic’s A.I. Really Make a Scientific Discovery on Its Own?

Learn more: prismscience.org

We talk about a big travel month (including Stephanie winning the George Sheldrick Award for Structural Science), federal funding in light of the upcoming turnover of US political representation, pre-prints, and the use of AI with agentic workflows for science and LLMs for writing. News Links: Derek Lowe's Blog: The Assault On Science Funding ContinuesSenate votes to block rule giving White House more control over researchEstimating global article processing charges paid to 14publishers for open access between 2019 and 2025 Preprints/Blogs: Atomic modeling of radiation damage in cryoelectron microscopy datasetsDynamic view of an allosteric intermediate in a positively cooperative dimerIncidental conformational switching in an allosteric enzymeAnthropic Protein Design PromptsThe Rise of Large Language Models and the Direction and Impact of US Federal Research Funding

We chat about a revolving door of consortium meetings for Jaime, follow up on the OMB proposed rule, two mini-protein kinase preprints, and differences between blogs and scholarly work. Preprints/Blogs: De novo design of selective kinase modulatorsSelective miniprotein inhibitors of Aurora-A kinase designed using interaction-motif scaffolding Ensemble refinement produces consistent R-free values but smaller ensemble sizes than previously reported News Links: Bethesda Declaration one year later The Public Rejects OMB's Federal Financial Assistance Rule

We chat about the conformational ensembles conference, NIH-proposed policy changes, 4!! preprints, & running. NIH news: OMB Proposal Blog Post Summary on OMB Proposal RFI to Cap the Number of Simultaneous Research Project Grants  Early Independence Award Preprints: Detection of residual native state entropy changes upon mutation in Fyn SH3 Protein-ligand binding kinetics are primarily controlled by the protein, not the ligand ESMFold2 sampleworks: A Modular Platform for Experimentally Guided Biomolecular Ensemble Generation

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 populations cryoAgent: An agentic workflow for robust and adaptive end-to-end cryo-EM image processing You need to make AI guidelines for your lab We’re Training Scientists for a World That No Longer Exists

diffUSE Project April Fools Blog NIH News: Funding Curve Drug Monkey 2025 Grant Report How the 2025 NIH grant terminations varied by researchers’ demographic groups Preprints: Intrinsic dataset features drive mutational effect prediction by protein language models Ribosome Molecular Aging Shapes Translation Dynamics AI Grad Student: Why I may ‘hire’ AI instead of a graduate student Vibe physics: The AI grad student

Topics: Olympics NIH Bureaucracy - Grants & Leaderships Preprints 12 episodes of TTPD! Claude Code & Slack Apps San Francisco Half Preprints: 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 Images Protein folding success depends on the direction and speed of polypeptide chain appearance Jeremy Reiter's gene list

Year in Review & 2026 Predictions Preprints: Rewriting protein alphabets with language models Fine-tuning protein language models on human spatial constraint yields state-of-the-art variant effect prediction Prachee 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 Reactions Preprint: 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 models Improved 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 Complexes Computational design of conformation-biasing mutations to alter protein functions Why do we still publish in scientific journals? - Pedro Beltrao's blog The diffUSE Project OpenADMET

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 AlphaFold Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity