The Tortured Proteins Department

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 Continues
• Senate votes to block rule giving White House more control over research
• Estimating global article processing charges paid to 14publishers for open access between 2019 and 2025

Preprints/Blogs:

• Atomic modeling of radiation damage in cryoelectron microscopy datasets
• Dynamic view of an allosteric intermediate in a positively cooperative dimer
• Incidental conformational switching in an allosteric enzyme
• Anthropic Protein Design Prompts
• The 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 modulators
Selective 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/Reopening
• Travels
• The impact of Jane Richardson
• AI Peer Review tools
• Preprint 1: Hit or Miss: Understanding Emergence and Absence of Homo-oligomeric Contacts in Protein Language Models
• 
  The Drain of Scientific Publishing
• 
  Big experiments are only big if they can fail