🔬ESM: The Bitter Lesson is Coming for Proteins - Alex Rives, BioHub

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Editor’s note: In our first BioHub pod with Priscilla and Mark they discussed their acquisition of EvoScale, led by Alex Rives, who is now Head of Science at BioHub. With ESM-1 they trained language models on millions of protein sequences drawn from across life, with a simple “next token” objective: predict the amino acids that have been randomly masked out, based on the context of the rest of the sequence. But they soon found that these models also learned biological structure and function, including properties the model had never been explicitly shown AND that this ability scales predictably with compute, leading to ESM2 and ESM3.Today, Alex announced ESMFold 2, an open scientific engine to power prediction, design, and discovery across protein biology.Building on Cryo-EM data (discussed in the CZI pod), ESMFold2 reports state of the art performance on protein interactions, especially antibodies, a critical modality for therapeutics, and evidence that inference time scaling is also working across five targets in cancer and immunology.In a nod to that other famous AI x protein folding project, they are also releasing an atlas of 6.8 billion proteins, and 1.1 billion predicted structures, which you can play around with on their website. We are honored to work with them for this huge release!One of the refrains we’ve heard on the Science pod has been that protein folding, materials design, cellular biology, etc. are very different problems from Language Modeling. They definitely are. Yet Alex Rives and the ESM team at BioHub just released a preprint and model, demonstrating that vanilla BERT-like transformer models trained on sufficiently large and diverse data sets can beat specialized models like AlphaFold3 on some of the hardest protein-related problems. Andrew White had a great segment in our first LS-Science episode that explained how mind blowing AlphaFold2 was when it was released in 2020: it suddenly solved problems on a GPU on your desktop that DESRes had built custom-ASIC supercomputer clusters to solve.