zlacker

That's interesting. Didn't realize that. It sounds like we're just working around slower computation speed.

In an fantasy world if we had infinite computation speed/space we'd be able to just model the force field and predict from there.

>>edmcnu+(OP)
Yes, that's a fantasy world. I explored this using the Exacycle system at Google and we did actually do a couple things that nobody else could have at the time, but even that extraordinary amount of computing power really is tiny. The problem is the "force field" isn't just the enthalpic contributions I listed above, but also depends intimately on much more subtle entropic details- things like the cost of rearranging water into a more ordered structure have to be paid for. Estimating those is very expensive- far worse than just enumerating over large numbers of proteins "in vacuo", and probably cannot be surmounted, unless quantum computing somehow becomes much better.

Instead, after spending an ordinate amount of Google's revenue on extra energy, I recommended that Google instead apply machine learning to protein structure prediction and just do a better job of extracting useful structural information (note: this was around the time CNNs were in vogue, and methods like Transformers didn't exist yet) from the two big databases (all known proteins/their superfamily alignments, and the PDB).

Note that this conclusion was a really hard one for me since I had dedicated my entire scientific career up to that point in attempting to implement that fantasy world (or a coarse approximation of it), and my attempts at having people develop better force fields (ones that didn't require as much CPU time) using ML weren't successful. What DeepMind did was, in some sense, the most parsimonious incremental step possible to demonstrate their supremacy, which is far more efficient. Also, once you have a trained model, inference is nearly free compared to MD simulations!

>>dekhn+09
That's interesting. Thanks for the info. They're getting better at Quantum. It's going to be fascinating to see the future of this field and all the potential medicine waiting to be discovered and the lifespan improvements and just sheer biological discoveries. It feels almost like the new panning for gold. :) It's pretty crazy to see how human advancement parallels computing power in so many areas.