Bernardo Pinto
@BernardoIPinto
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Postdoc @uchicago. Working on ion channel biophysics. 🦑 @pintobi.bsky.social
Joined October 2011
1/ New paper! I have used AlphaFold2 to uncover the structural basis for voltage gating and drug binding in the Shaker family of potassium channels - key players that regulate neuronal excitability and a target for neurological diseases treatment. 🧵
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The #AlphaFold 3 model code and weights are now available for academic use. We @GoogleDeepMind are excited to see how the research community continues to use AlphaFold to address open questions in biology and new lines of research. https://t.co/kVB9hWJZTI
github.com
AlphaFold 3 inference pipeline. Contribute to google-deepmind/alphafold3 development by creating an account on GitHub.
We love the excitement & results from the community on AlphaFold 3 and are doubling the AF Server daily job limit to 20. Happy to also share that we're working on releasing the AF3 model (incl weights) for academic use, which doesn’t depend on our research infra, within 6 months.
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Here's what the website of a $1 trillion market cap company looks like:
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eLife latest in string of major journals put on hold from Web of Science. https://t.co/TXGCKD6BNB
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9/Read the full paper here: https://t.co/iODdF598pp You can check the closed state model and associated data here: https://t.co/eXg5HwZzJw Currently seeking opportunities to establish my own research program. Open to opportunities! DMs open for: Collaborations & Faculty positions
zenodo.org
Data and models for paper "Structural Basis for Voltage Gating and Dalfampridine Binding in the Shaker Potassium Channel Revealed by Closed-State Model"
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8/A huge thanks to my mentor Francisco (Pancho) Bezanilla for his support throughout this work. This was only possible thanks to the amazing research environment at @UChicagoMed @UChicagoBMB! Also grateful to @UChicagoRCC and @GoogleCloud for computational support.
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7/ Beyond contributing to tackle a decades-old puzzle in neuroscience, this work provides a structural framework for developing new, more selective and efficient drugs targeting voltage-gated channels. This opens new possibilities for treating conditions from MS to epilepsy.
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6/ I found where the drug dalfampridine (4-AP) binds, a hydrophobic pocket in the closed state. This explains why 4-AP helps Multiple Sclerosis patients: it stabilizes the closed state by binding to this pocket, diminishing potassium conductance and improving nerve conduction.
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5/ A critical step in this activation mechanism is the breakage of a backbone hydrogen bond in the pivot point between the S4-S5 linker and S5 helix, like a molecular latch. Breaking this latch with a proline mutation made the channel much easier to open - as the model predicted!
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4/ So how does the channel work? Three moving parts: R4 (the voltage sensor), S4-S5 linker (the coupler), and S6 helices (the gate). When R4 moves down, the sensor push the S4-S5 linker that causes the C-terminus of the S6 rotate and contract closing the channel.
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3/ This R4down state was crucial because R4 needs to be up for the channel to open. So, when I used the R4down conformation to model the whole channel and Voilà the models generated have a closed pore. And the results are in agreement with previous accessibility measurements.
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2/ Voltage sensors are molecular voltmeters. They detect changes in membrane voltage by moving charged arginines up and down the membrane. I used AlphaFold2 MSA subsampling to explore different of the voltage sensor and identified a state in which the last arginine (R4) is down.
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Trumps only sold about $10mln of their crypto token — target was $300mln
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“Very Novel!” 😂 I love his enthusiasm, please someone give these attendees a poster prize! 🏆 🐦 @SfNtweets
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John Jumper went from getting a PhD to getting a Nobel Prize in just seven years!
BREAKING NEWS The Royal Swedish Academy of Sciences has decided to award the 2024 #NobelPrize in Chemistry with one half to David Baker “for computational protein design” and the other half jointly to Demis Hassabis and John M. Jumper “for protein structure prediction.”
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Most of the reporting on scam compounds--where thousands of people are trafficked to run crypto scams--wouldn't have happened without @MechDara1. He should win journalism prizes. Instead he's imprisoned in Cambodia on bogus charges. Free Dara! Reporting is not a crime!
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I'm really mad about how fast my life went from MySpace to MYCHART.
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My new investigation for @newsfromscience: Did a top @NIH official manipulate Alzheimer's/Parkinson’s research for decades? Neuroscientist Eliezer Masliah found to engage in scientific misconduct; 132 of his papers fall under suspicion https://t.co/gF4fcjDipJ
science.org
Agency announces research misconduct finding for neuroscientist Eliezer Masliah as scores of his papers fall under suspicion
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Where do new organs come from? In paired studies, we explore walking fish with "legs" to learn about the evolution of new traits. @MBLScience, @CellPressNews, @CurrentBiology - https://t.co/2z2q31Vaz5 - https://t.co/CxfhKYtPxB
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Cassava Sciences Inc, Remi Barbier, & Dr. Lindsay Burns, will pay more than $40M to settle charges related to misleading statements made about the results of a Phase 2 clinical trial for the company’s purported therapeutic for the treatment of Alzheimer’s. https://t.co/GdAo3MMytZ
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