Video wird geladen...

Video konnte nicht geladen werden

Zur Startseite

The possibilities for AI-powered protein design are endless! In this case study we show how we used BindCraft to engineer a programmable maltose biosensor from scratch, including wet lab validation at Adaptyv of course. We envision a future where every biologist can make their own bespoke protein tools to...

52,115 Aufrufe • vor 11 Monaten •via X (Twitter)

0 Kommentare

Keine Kommentare verfügbar

Kommentare vom Original-Post werden hier angezeigt

Ähnliche Videos

What seemed like an intractable problem is now possible: To design proteins with a specified nonlinear mechanical response, capturing complex folding and unfolding mechanisms in singe and few-shot computations. We present ForceGen, an end-to-end algorithm for de novo protein generation based on nonlinear mechanical unfolding responses. Rooted in the physics of protein mechanics, this generative strategy provides a powerful way to design new proteins rapidly, including exquisite and rapid predictions about their dynamical behavior. Proteins, like any other mechanical object, respond to forces in peculiar ways. Think of the different response you'd get from pulling on a steel cable versus pulling on a rubber band, or the difference between honey and glass. Now, we can design proteins with a set of desirable mechanical characteristics, with applications from health to sustainable plastics. The key to solving this problem was to integrate a protein language model with denoising diffusion methods, and using accurate atomistic-level physical simulation data to endow the model a first-principles understanding. ForceGen can solve both forward and inverse tasks: In the forward task, we can predict how stable a protein is, how it will unfold and what the forces involved are, all given just the sequence of amino acids. In the inverse task, we can design new proteins that meet complex nonlinear mechanical signature targets. Read the paper, led by LAMM@MIT postdoc Bo Ni, published in Science Advances: Why do we care about the mechanics of proteins? The mechanics of proteins are critical elements of many living systems - as evidenced in many studies of mechanobiology. Through evolution, nature has presented a set of remarkable protein materials with unique mechanical functions like elastins, silks, keratins or collagens that play crucial roles in biology. However, going beyond natural designs to discover proteins that meet specified mechanical properties remains challenging. So far, the only way to do this was to use existing evolutionary concepts or to manually alter proteins. With our new generative model we can directly design proteins to meet complex nonlinear mechanical property-design objectives. ForceGen leverages deep knowledge on protein sequences from a pretrained protein language model and maps mechanical unfolding responses to create proteins. Via full-atom molecular simulations for direct validation from physical and chemical principles, we demonstrate that the designed proteins are de novo, and fulfill the targeted mechanical properties, including unfolding energy and mechanical strength, and a detailed unfolding force-separation curves. ForceGen offers rapid pathways to explore the enormous mechanobiological protein sequence space unconstrained by biological synthesis, to enable the discovery of new protein materials with superior mechanical properties. B. Ni, D.L. Kaplan, M.J. Buehler, ForceGen: End-to-end de novo protein generation based on nonlinear mechanical unfolding responses using a language diffusion model. Sci. Adv. 10, eadl4000 (2024). DOI: 10.1126/sciadv.adl4000 Codes and model weights available Hugging Face: David Kaplan

Markus J. Buehler

47,242 Aufrufe • vor 2 Jahren

Today, we expand zero-shot drug design beyond binding to the design of multifunctional medicines, the intracellular proteome, and state-of-the-art atomic precision with our model, JAM-2. In a new report (below), we show: 1. The first drug-grade, fully computationally designed multispecific antibodies against five peptide-MHCs: Routine picomolar T-cell activation/cell-killing EC50s, >100-fold selectivity, and drug-like developability 2. The first fully generatively designed, drug-grade dual-variant KRAS G12 multispecifics: They recruit primary T-cells from human donors to kill G12V and G12C presenting cells at pM to single-digit-nM potency, completely sparing wild-type. 3. Atomic accuracy, from sequence alone: Angstrom-level agreement between Cryo-EM and JAM-2 de novo designs, requiring only target sequences (not structure) as input. 4. Unrivaled speed with an AI-native in-house wet lab: Designed, built, and tested five programs in one parallelized campaign, end-to-end in-house in ~6 weeks. 5. A higher validation bar for AI-generated drug candidates: In a field increasingly rife with hype and uneven standards of proof, we provide the highest quality public wet-lab validation of AI-designed antibodies to date. We share experimental methods in full, and invite folks to adopt and build on these standards. Truly individualized therapies will be the most important contribution of AI in drug design. These advances help accelerate this future.

Nabla Bio

179,160 Aufrufe • vor 1 Monat

AI instead of UI The last few years radically changed how we think about digital products & product design process in general. What we are witnessing right now is a transition where AI is no longer just a feature; it is becoming the infrastructure of interaction. For decades, UI design was rooted in the concept of “Happy Path,” a series of static, linear screens (routes from A to B) designed to funnel users toward a goal. This “one-size-fits-all” approach assumes that all users have the same mental model, which is far from the truth. The rise of AI tools like ChatGPT and Gemini is showing that we are moving into an era of Generative Interfaces. Instead of a designer pre-determining every button and menu, the interface is synthesized in real-time based on user actions. Back in 2019, Gleb Kuznetsov and I were working on the concept of morphing Interface, the idea of a UI that adapts its structure based on user intent. The great thing about this UI is that it was highly dynamic: different users saw different content/contextual actions based on their behavior. This concept was crazy in 2019, but it is highly relevant to the modern state of the product design process. And I strongly believe that it represents the future of UI design. We will move beyond the “AI chatbox" crutch Yes, many products today treat AI as a sidecar (think of Copilots or chatbots pinned to the side of a traditional dashboard), but this is a transitional phase. Why? Because adding a chat window to a 20-year-old software layout is like putting a jet engine on a horse-drawn carriage. That's why the future isn't "AI as an add-on"; it is AI as the Operating System. AI will power generative interfaces that are rooted in anticipatory design: UI won’t wait for a command; it will surface tools based on the user's current environmental context and historical behavior. This evolution changes the very nature of product design, and we will move away from designing pages/screens and toward designing systems of logic.

Nick Babich

53,581 Aufrufe • vor 6 Monaten