The Tortured Proteins Department

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

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

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

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

- 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

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