Specialized Equivariant Architectures Vastly Outperform Simple Transformers in Molecular ML
Gabriele Corso · 🔬Generating Molecules, Not Just Models · Feb 12, 2026 · at 26:51
Gabriele Corso, co-founder of Boltz and MIT PhD graduate, discusses whether the 'bitter lesson' applies to biomolecular structure prediction models.
0:00 / 0:30exact quote · 30.5s
▶ Watch the full episode on YouTube → 720p mp4 · rendered on demand · StarZero watermark
“This field is one of the I would argue very few fields in applied machine learning where we still have kind of architecture. They are Very specialized. And, you know, there are many people that have tried to replace these architectures with, you know, simple transformers. And, you know, there is a lot of debate in the field, but I think kind of the most of the consensus is that, you know, the performance that we get from the specialized architecture is vastly superior than what we get through a single transformer.”
quote is from the automated transcript, cleaned for reading: filler sounds and stutters are removed, nothing is rephrased. names can be misheard (the analysis reads context, assessments check outside sources). how →
More from Gabriele Corso
Boltz-1 Was the First Open-Source Model Matching AlphaFold 3 Accuracy
“We went ahead and built Pulse One, which was the first fully open source kind of model to approach the level of accuracy of half-fold-free.”
Generative Molecular Models Exhibit Dramatic Inference-Time Compute Scaling
“These days we're seeing kind of pretty dramatic inference time scaling of these models where, you know, the more you run them, the better the results are.”
Model Structural Confidence Is a Poor Predictor of Binding Affinity
“Unfortunately, confidence is not a very good predictor of affinity.”
Most Protein Design Validation Uses Targets With Training Data Overlap
“One of the things that, you know, we found, ah, with the field was that a lot of the validation, especially outside of the validation that was done on specific problems, was done on targets that have a lot of, you know, known interactions in, in the training d…”
Boltz Achieved Nanomolar Binders on Two-Thirds of Zero-Homology Targets
“And the very cool thing that we saw was that on two-thirds of those targets, we were able to, from these 15 designs get nanomolar binders.”
AlphaFold Resolves Protein Structures Using Dijkstra-Like Pairwise Distance Decoding
“From this evolutionary information about potential contacts, Then it's almost as if the model is sort of running some kind of, you know, Diestro algorithm, where it's sort of decoding, okay, these have to be closed, okay, then if these are closed and this is c…”