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Comment by timr

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Comment by timr

Well first off: molecular screening (which is basically what you're describing) is inadequate for drug discovery. There are too many other factors that matter: water positions, molecular flexibility, short and long-range electrostatics, entropy loss, coordinating ions, and more. You need not only the "pocket", but an accurate model of the system's conformational change over time, to have any hope of understanding binding energetics. It's a bigger problem for small molecule drug discovery than biologics, but it still matters.

That said, we have extremely well-refined force fields that attempt to model the underlying physics, and still fail to do this well. There's absolutely no reason to believe that a generic LLM will bring anything to the table that improves the situation. Even with the hand-wavy assertion that we (somehow) get "lots and lots of data", and somehow train a purpose-built model to do the same, it's kind of like saying that we could turn a minivan into a formula one car with enough effort. Different tools for different jobs.

I actually do believe that informatics approaches will be helpful given lots of system-specific data, but when I say that, I mean "a bespoke neural energetic model that is trained specifically for some molecular system down to customized force-field parameters", not "Claude".

So sure, maybe Anthropic will invest lots of time and money and energy into making these kinds of molecular simulation models, which they can then use for high-throughput screening experiments. But even if they do all of that, there's still no guarantee that they'll bring anything to the party that hasn't been done before...because this is the lowest-value step of drug discovery, and a model like that won't tell you if your drug is going to be toxic, or have off-target effects, or have metabolic problems, or...a million other things, which are what kill drug programs in phase 1 and beyond.

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