Mastermind

Travels, US election results, preprints & SPOILER ALERT: You Can See Everything discussion at the end of the pod.Preprints: Iterating diffuse scattering protocols in parallel leads to reproducible, high-quality data from Mac1Phase separation reshapes the conformational energy landscape of a chaperone to prime its activityMassively parallel quantification and prediction of monomeric protein yield in Escherichia coliClaude vault particles

We talk about ANOTHER big travel month, federal fights over science funding, preprints, and the intersection of AI and scientific discoveriesNews Links:Inside the US military's plan to tap huge sums from the NIHNew lawsuit accuses Trump administration of blocking NIH grants as form of censorshipTrump asked budget chief to draft order bringing health research funding under his controlPreprints: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 agentsDid 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 2025Preprints/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 scaffoldingEnsemble refinement produces consistent R-free values but smaller ensemble sizes than previously reportedNews Links:Bethesda Declaration one year laterThe 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 ProposalRFI to Cap the Number of Simultaneous Research Project Grants Early Independence AwardPreprints:Detection of residual native state entropy changes upon mutation in Fyn SH3Protein-ligand binding kinetics are primarily controlled by the protein, not the ligandESMFold2sampleworks: 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 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