Opinion
Specialized Equivariant Architectures Vastly Outperform Simple Transformers in Molecular ML
“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 t…”
Assertion Supported
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.”
Assertion Supported
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.”
Insight
Model Structural Confidence Is a Poor Predictor of Binding Affinity
“Unfortunately, confidence is not a very good predictor of affinity.”
Assertion Not checkable as stated
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…”
Assertion Supported
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.”
Insight
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…”
Assertion Supported
AlphaFold Models Have Fewer Parameters but Higher Compute Costs Than LLMs
“They, in terms of parameters, are actually not very big. They are definitely below a billion parameters. You know, if you're here these days in LLM space, you know, a model with less than a billion parameters, you'd think can't do anything. But on the other ha…”
Assertion Supported
AlphaFold 3 Still Holds an Edge in Antibody-Antigen Prediction
“I would still say that, you know, even to this day, there are, you know, some specific instances where AlphaFold III works better. I think one common example is antibody antigen prediction, where, you know, AlphaFold III still seems to have an edge in, in many…”
Insight
Open-Sourcing Models on GitHub Is Insufficient for Biotech Industry Adoption
“One of the reasons why we realized that Bolts needed to be a company, it couldn't just be an academic project, is that putting a model on GitHub is definitely not enough To get, you know, chemists and biologists, you know, across, you know both academia, biote…”
Insight
AI-Designed Proteins and Molecules Are Not Ready-to-Use Drugs
“When we say that we design new proteins, or we say that we design new molecules, you know you know, go and bind these particular targets. We should be very clear. You know, these are not drugs. You know, these are not things that are ready to be put into a hum…”
Insight
Diffusion Generates Distinct Structures While Regression Averages Them
“What's going to happen in a regression model is that, you know, I'm going to try to make an average of those different kind of answers that I had in mind. When you have a generative model, what you're going to do is, you know, sample all these different answer…”
