Biophysical chemist, redox biology, professor at UCSB, dad, husband, and part-time adventurer
Time to clean…
Watched October Sky last night and 1. I think this had a significant influence on me as a kid becoming a scientist and 2. We can capture this energy again as a country. A politician who can tap into this will do well.
A totally predictable/avoidable outcome.
www.science.org/content/arti...
U.S. government has lost more than 10,000 STEM Ph.D.s since Trump took office
A Science analysis reveals how many were fired, retired, or quit across 14 agencies
We need to get of our scientific preconceived notions!
Here are my scientific preconceived notions!
open.spotify.com/episode/7vfd...GET IN, DORKS!
The stakes are high and we have a LOT to stand up for in 2026.
Join us on March 7th, 2026!
www.standupforscience.net/march7
Want to host an event in your area? Sign up here:
fight2win.standupforscience.net/sign_up/14434/
#Standupforscience #takebackourscienceIt's finally out! Great work Ben, Sichu, Sarah, Brett, Ian and Samer for the wonderful science and effort here. The role of the N5 environment in tuning flavin reduction potentials.
pubs.acs.org/doi/10.1021/...
Measurement and Control of Crossed Potentials in a Flavoprotein
Flavoproteins constitute 1–3% of prokaryotic and eukaryotic proteins, functioning as electron transfer agents, catalysts, and sensing or regulatory modules. Their versatility as redox-active proteins stems from the tunability of the flavin cofactor’s one- and two-electron reduction potentials via interactions with the protein scaffold. Although several mechanisms have been proposed to explain how the flavin-binding pocket modulates redox thermodynamics, a holistic model enabling interpretation and prediction remains to be established. In this study, we investigate how the flavin N5 environment influences the redox properties of the flavin mononucleotide cofactor in the “improved” light-oxygen-voltage (iLOV) sensing protein using site-directed mutagenesis, redox titrations, and hybrid quantum mechanical molecular mechanical (QM/MM) methods combined with classical alchemical free energy simulations. Mutating the residue Q103, which interacts with the flavin N5 and O4 atoms in the X-ray crystallographic structure, exerts a modest <35 mV effect on the overall two-electron reduction potential, but significantly alters the potential separation of the two one-electron couples (potential crossing) by up to 168 mV. QM/MM and free energy calculations reveal that water penetration into the flavin-binding pocket near N5 and O4 largely explains the trend in reduction potentials among the mutants. The results suggest a molecular mechanism of flavin tuning in which hydrogen bonding to the neutral semiquinone, either directly by the side-chain or a protein-penetrating water, contributes significantly to the potential crossing. These findings establish quantitative experimental benchmarks for theoretical models and advance a molecular mechanism for redox tuning in flavoproteins.
That tech oligarchs are noisy and incensed about the remote possibility of a wealth tax and utterly silent about the murder of a man who was only using the phone they invented to chronicle the thuggish government goon squads should tell you everything about these desiccated souls.
ICE Kills Another American
YouTube video by Takes™ by Jamelle Bouie
Thanks
@nature.com for the beautifully depressing article!
www.nature.com/immersive/d4...
US science after a year of Trump: what has been lost and what remains
A series of graphics reveals how the Trump administration has sought historic cuts to science and the research workforce.
“The border between democracy and fascism is the least defended border in the world” Ivan Krastev
Visuals dept. at NYT is crushing it recently.
www.nytimes.com/interactive/...
Opinion | How Trump Has Used the Presidency to Make at Least $1.4 Billion
The president took an oath to serve the American people. Instead, he’s focused his second term on enriching himself and his family.
Breakfast made for kiddo: blueberry sourdough French toast, a poached egg, and chicken sausage.
Kiddo ate: pineapple
Teaching glycolysis this week in my biochemistry class, and cannot recommend this article enough. I really wish I had been taught this critical pathway from a perspective of (bio)chemical logic, rather than memorizing ten enzymatic reactions...
www.nature.com/articles/nch...Interesting article. Two takeaways: (1) adjusted for inflation, Chemical BS and MS incomes have converged! and (2) again adjusted for inflation, PhDs are down 6K from 2005!
cen.acs.org/careers/sala...
US chemistry worker salaries grew 9% in 2024: ACS member survey
The median salary rose to $120,000, with higher wages in New England and on the West Coast as well as in chemical engineering
Under-discussed point, but I wonder if trump called the parents of the US service men/women who were injured during the Venezuela operation? Wonder what the justification was to them, and if they are enthusiastic.
I don’t know, felt right.
Rough year for science, among other aspects of life...
www.science.org/doi/10.1126/...
Breakdowns of the year
What went wrong in the world of science
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In the spirit of the season “shitter’s full!”
This year’s Presidential Christmas card.
Strange post after my last,but here goes. A lot of measures of a countries wellbeing are on a scale. There are a few that are Boolean. I would contest that children experiencing double tap school shooting experiences is, and close to are there elections.
Daycare cancelled, so we’re making the best of it. Aspect ratio will never be the same 😭
Very cool article but some pretty scary potential consequences.
www.nytimes.com/interactive/...
How Did the C.I.A. Lose a Nuclear Device in the Himalayas?
A plutonium-packed generator disappeared on one of the world’s highest mountains in a covert mission that the U.S. will not talk about.
New group photo! Yes, we have a bamboo grove on campus.
Very cool structure of the colibactin DNA cross-link from the Harvard/UMinn collab here. How do you validate that this is the causative agent in vivo remains a substantial challenge, but seems pretty convincing.
www.science.org/doi/10.1126/...
The specificity and structure of DNA cross-linking by the gut bacterial genotoxin colibactin
Accumulating evidence has connected the chemically unstable, DNA-damaging gut bacterial natural product colibactin to colorectal cancer, including the identification of mutational signatures that are ...
Really love historical science, and this account of the development of alchemical free energy calculations is great! Also very top of mind, as our collaborator Samer Gozem used these methods to estimate redox potentials in our model flavoprotein.
pubs.acs.org/doi/10.1021/...
The Dawn of Alchemical Free-Energy Methods in Biomolecular Simulations
From the onset of fundamental statistical mechanical constructs formulated in the late 19th century, alchemical free-energy methods slowly emerged and transitioned to become operational tools of biomolecular simulation applicable to a wide range of problems including protein–ligand binding for drug discovery research. This article reconstructs how statistical mechanical approaches such as thermodynamic integration and free-energy perturbation were reconfigured in the early 1980s to address the complexities of increasingly heterogeneous biomolecular systems. Drawing on oral history interviews and primary literature, the study examines the technical, institutional, theoretical, and infrastructural conditions under which these methods were implemented, and it became progressively operational. These conditions encompassed the consolidation of lab-specific software infrastructures, the formulation of practical simulation protocols, and essential statistical mechanical clarifications. From this perspective, the progress of free-energy methods proceeded less from a unified convergence than from an iterative troubleshooting process of alignment involving practical and theoretical considerations. The aim of the present article is to offer a historically grounded account of how free-energy techniques acquired practical and functional reliability.
Great article from Hegazy and Richards! Role of phosphates of the nucleotide substrate in phosphite dehydrogenase. Love these classic enzymology studies. To the transition state, and beyond!
pubs.acs.org/doi/10.1021/...
Enzyme Architecture: Activation of Phosphite Dehydrogenase-Catalyzed Hydride Transfer by NAD+ Cofactor Fragments
We report the results of experiments to test the hypothesis that binding energy from the adenosine diphosphate (ADP) fragment of the NAD+ cofactor is utilized to drive a protein conformational change...
Decisions…
Trump Pauses All Asylum Applications and Halts Visas for Afghans
The beast in me was immaculate. Acting could be a little off (not you Mrs. Danes and Mr. Rhys) but Japanese joinery writing.
Interested in a postdoc studying non-equilibrium redox biology in the Greene lab? The Irving S. Sigal Postdoctoral Fellowship is a great opportunity to be recognized and to provide the financial support for exciting research. DM me if you or anyone you know is interested. Nomination-based.
Cobalt doing nickel-like chemistry in acetyl-CoA synthase (ACS) in a MOF?!?!? Very cool. I wonder if anyone has looked at acetate production from ACS at elevated CO (or isotope pulse-chase)?
www.science.org/doi/10.1126/...
Multigas adsorption with single-site cooperativity in a metal–organic framework
Cooperative gas adsorption in metal–organic frameworks (MOFs) is a rare phenomenon that generally involves long-range communication between multiple binding sites. We demonstrate a MOF containing coba...
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Can confirm. A sad state, but we would be doing a disservice to admit people we can't pay for. Want more R&D in the US? Pay for it. The ROI is incredible...
www.nature.com/articles/d41...
US PhD admissions shrink as fears over Trump’s cuts take hold
Some doctoral programmes are admitting no students at all amid uncertainty about federal science funding.
