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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

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/10.1101/2025.03.27.644168v1

Enthalpy-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=1

Conserved energetic changes drive function in an ancient protein fold- https://www.biorxiv.org/content/10.1101/2025.04.02.646877v1

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.pdf
AF2χ: Predicting protein side-chain rotamer distributions with AlphaFold2:
https://www.biorxiv.org/content/10.1101/2025.04.16.649219v1.full.pdf

- 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

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

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

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!)

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
  

Topics:

• Compact for Academic Excellence in Higher Education
• Government Shutdown
• HHMI's new open science policies
• Shrinking PhD pools
• The Nobel Prizes
• The Bear
• TLOS Reactions

Preprint: Experiment-guided AlphaFold3 resolves accurate protein ensembles

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

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