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Exclusive: Charm Therapeutics applies AI to complex protein interactions, locking down $50M A round

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Charm Therapeutics applies AI to complex protein interactions, locking down $50M A round

#Charm #Therapeutics #applies #complex #protein #interactions #locking #50M

The world of AI-powered drug discovery keeps expanding as the capabilities of machine learning grow. One approach that seemed unthinkable just a few years ago is simulating the complicated interplays of two interlocking molecules — but that’s exactly what drug designers need to know about, and exactly what Charm Therapeutics aims to do with its DragonFold platform.

Proteins do just about everything worth doing in your body, and are the most frequent targets for drugs. And in order to create an effect, you must first understand that target, specifically how the chain of amino acids making up the protein “folds” under different circumstances.

In the recent past this was often done with complex, time-consuming X-ray crystallography, but it has recently been shown that machine learning models like AlphaFold and RoseTTAFold are capable of producing results just as good but in seconds rather than weeks or months.

The next challenge is that even if we know how a protein folds in its most common conditions, we don’t know how it might interact with other proteins let alone novel molecules made specifically to bind with them. When a protein meets a compatible binder or ligand, it can transform completely, since small changes can cascade and reconfigure its entire structure — in life this leads to things like a protein opening a passage into a cell or exposing a new surface that activates other proteins, and so on.

“That’s really where we have innovated: we have built DragonFold, which is the first protein-ligand co-folding algorithm,” said Laskh Aithani, CEO and co-founder of Charm Therapeutics.

“Designing drugs that bind to the disease-causing protein of interest very tightly and selectively (i.e., avoid binding to other similar proteins that are required for normal human functioning) is of paramount importance,” he explained. “This is done most easily when one knows how exactly these drugs bind to the protein (the exact 3D shape of the ligand bound to the disease-causing protein). This allows one to make precision modifications to the ligand such that it can bind more tightly and more selectively.”

You can see a representation of this situation at the top of the article: The small green molecule and the purple protein fit together in a very specific way that is not necessarily intuitive or easy to predict. Effective and efficient simulation of this process helps screen billions of molecules, similar to earlier processes that identified drug candidates but going further and reducing the need to experimentally check whether they interact as expected.

To accomplish this, Aithani tapped David Baker, designer of the RoseTTAFold algorithm among many others and head of an influential lab at the University of Washington, to be his co-founder. Baker is well known in academia and industry as one of the leading researchers in this area, and he has published numerous papers on the subject.

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Charm Therapeutics co-founders Laskh Aithani (left) and David Baker. Image Credits: Charm Therapeutics

Shortly after it was shown that algorithms could predict protein structures based on their sequence, Baker established they could also “hallucinate” new proteins that acted as expected in vitro. He’s very clearly on the leading edge here. And he won a $3 million Breakthrough prize in 2020 — definitely up to being a technical co-founder. Aithani also proudly noted the presence of DeepMind veteran Sergey Bartunov as director of AI and former pharma research lead Sarah Skerratt as head of drug discovery.

The $50 million A round was led by F-Prime Capital and OrbiMed, with participation from General Catalyst, Khosla Ventures, Braavos and Axial. While such large amounts are not uncommon for software startups, it should be noted that Charm is not stopping at building the capability of characterizing these protein-ligand interactions.

The company’s early-stage funding was used to build the model, but now they’re moving on to the next step: positive identification of effective medications.

“We have the initial version [of the model] ready, and that has been validated in-silico,” Aithani said. “Over the coming quarters, we are validating it experimentally. Note that the ‘product’ will mainly be for internal use to help our own scientists discover potential medicines that we own 100% of the rights to.”

Ordinarily the testing process involves wet-lab screening of thousands upon thousands of candidate molecules, but if it works as advertised, DragonFold should massively cut down on that number. That means a relatively small lab with a relatively small budget can conceivably home in on a drug that a few years ago might require a major pharma company investing hundreds of millions.

Considering the profit profile of a novel drug, it’s no surprise that the company has attracted this kind of investment: a few tens of millions is a drop in the bucket compared with the R&D budget of any big biotech research company. All it takes is one hit and they’re laughing. It still takes a while, but AI drug discover shortens timelines as well — so expect to hear about their first candidates sooner rather than later.

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Exclusive: Ford Bronco Heading to Europe in 'Limited' Quantities – CNET – TalkOfNews.com

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Ford Bronco Heading to Europe in 'Limited' Quantities     - CNET

#Ford #Bronco #Heading #Europe #039Limited039 #Quantities #CNET

The auto industry is rife with forbidden fruit, whether it’s Americans lusting over small European cars or Europeans jonesing for high-horsepower American metal. But, as Europe is about to find out, not all fruit stays forbidden forever.

Ford on Monday announced that it will bring the Bronco SUV to Europe. Ford didn’t offer up too many details just yet, saying only that the Bronco will arrive in certain left-hand-drive markets, and that quantities will be “strictly limited.” It should go on sale in late 2023, so Europeans keen to get their hands on one will have some time to figure out how to do that.

By the sounds of Ford’s press release, the EU-market Bronco won’t be much, if at all different from the US-spec Bronco. All the off-road capability is still there, all the cabin tech remains the same, which means it should function as a pretty potent competitor to the Land Rover Defender. A veritable Sears catalog of accessory parts is available for owners to personalize their vehicles, as well.

It’s unclear which of the Bronco’s many variants will show up in Europe. In the US, we’re privy to eight different models, from the base model all the way up to the extra-chunky Raptor. Nearly all are available in a choice of two- or four-door versions, and a 2.3-liter I4 and 2.7-liter twin-turbo V6 are available at different points in the lineup, as well. Autocar’s report casts doubt on the 3.0-liter V6 Bronco Raptor making it to Europe, but hey, some Broncos are better than no Broncos, right?

Late 2023 isn’t exactly around the corner, so it’s likely that Ford will trickle out more information about European Broncos as we creep closer to the targeted on-sale date.

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Exclusive: Core Scientific, a top bitcoin miner responsible for nearly 10% of the network's hash rate, sold 7,202 mined BTC for $167M in June and now holds 1,959 BTC (David Pan/Bloomberg) – TalkOfNews.com

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Core Scientific, a top bitcoin miner responsible for nearly 10% of the network's hash rate, sold 7,202 mined BTC for $167M in June and now holds 1,959 BTC (David Pan/Bloomberg)

#Core #Scientific #top #bitcoin #miner #responsible #network039s #hash #rate #sold #mined #BTC #167M #June #holds #BTC #David #PanBloomberg


David Pan / Bloomberg:

Core Scientific, a top bitcoin miner responsible for nearly 10% of the network’s hash rate, sold 7,202 mined BTC for $167M in June and now holds 1,959 BTC  —  Core Scientific Inc., a top crypto miner, sold the bulk of its Bitcoin holdings in June as a steep drop in digital assets squeezes finances for even the leaders of the industry.


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Exclusive: Check Out This Drag Racing VW Beetle EV – TalkOfNews.com

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Check Out This Drag Racing VW Beetle EV

#Check #Drag #Racing #Beetle

The Late Brake Show

While it may sound a bit odd, people really like to convert old VW Beetles into electric drag-racers. The practice goes back twenty years, and back in 2011, two brothers shocked the world with their Black Current III electric Beetle. Now they’re back with an even more ridiculous car, the “V8-killing” Black Current IV.

Note: Several outlets are clinging to this story under false pretenses. The modified VW Beetle EV doesn’t have 6,500 horsepower—that rating is both outrageous and plainly incorrect. ‘The Late Brake Show’ acknowledges that it made a mistake, but other publications aren’t doing their due diligence.

We decided to share this story because it’s really freakin’ cool. It highlights a scene of enthusiasts who are integral to the rise of EVs. The horsepower doesn’t matter.

While previous Black Current EVs were based on very old VW Beetles, the new model is a heavily modified 2013 mk2 New Beetle. It now has a full carbon-fiber body, plus a custom 22kWh battery pack and 800V architecture. Notably, it runs on a total of four inverters, which diligently control the rotation speed of four permanent magnet Axial flux AC three-phase motors.

Brothers Olly and Sam Young, who built the Black Current IV, believe that it can run a quarter-mile in seven seconds or less. That would make it the “world’s quickest” electric vehicle, which is shocking, given that it’s a modified Beetle and it’s street legal. (The Young brothers haven’t brought this thing to top speed yet, so we can’t confirm how fast it actually moves.)

For reference, the Tesla Model S Plaid recently completed a 9.4-second quarter mile. And the current world-record holder, the Rimac Nevera, made its trip in 8.52 seconds.

This shouldn’t come as much of a surprise—the old Black Current III was a record-setter back in 2011, despite the fact that it ran on a repurposed milk-float motor (an electric motor from a UK milk delivery truck). The only reason why Olly and Sam Young started working on this new Black Current VI is because the previous model crashed at 140 MPH during a drag race in 2017.

Anyway, you should watch the above video made by The Late Brake Show. It covers the Black Current VI and its history in more detail than I’ve provided. Plus, it’s a video, and I know you want to see this weird drag-racing EV.

Source: The Late Brake Show

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