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I wasn't expecting to see David Baker in the list (just Demis and John). But I'm really glad to see it... David is a great guy. At CASP (the biannual protein

by dekhn 2y ago

I wasn't expecting to see David Baker in the list (just Demis and John). But I'm really glad to see it... David is a great guy. At CASP (the biannual protein structure prediction competition) around 2000, I sat down with David and told him that eventually machine learning would supplant humans at structure prediction (at the time Rosetta was already the leading structure prediction/design tool, but was filled with a bunch of ad-hoc hand-coded features and optimizers). he chuckled and said he doubted it, every time he updated the Rosetta model with newer PDB structures, the predictions got worse. I will say that the Nobel committee needs to stop saying "protein folding" when they mean "protein structure prediction".

jboggan 2y ago
The models and tools designed for the CASP competition were an example of running around the solution space at a glacial pace and getting stuck in local minima. I can't speak for Rosetta by my labmates had fairly successful tools that usually ranked right behind Baker's lab, and they were plagued by issues where the most successful models had impossible or idiosyncratic terms in them. For example, a very successful folding model had the signs reversed on hydrophobic and some electrostatic interactions. It made no sense physically but it gave a better prediction than competing models, and it was hard to move away from because it ranked well in CASP.
- dekhn 2y ago
  Which model had the signs reversed? Yes, CASP was prone to getting stuck in local minima. I think the whole structure prediction field had become moribund.
throwawaymaths 2y ago
Refreshingly good. Bakers "early" (not really early, but earlier than AlphaFold) work (having humans with no background solve folds) really laid the groundwork to proving that heuristic methods were likely to outperform physical forcefield and ab initio/DFT methods for structure prediction. And AI structure prediction if nothing else is heuristic protein folding.
siver_john 2y ago
They had to put David Baker on here, his work on protein design if nothing else was ground breaking. I've expected him to win it at some point in a, it's not a matter of if but of when.
deleted 2y ago
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by dekhn 2y ago

jboggan 2y ago

The models and tools designed for the CASP competition were an example of running around the solution space at a glacial pace and getting stuck in local minima. I can't speak for Rosetta by my labmates had fairly successful tools that usually ranked right behind Baker's lab, and they were plagued by issues where the most successful models had impossible or idiosyncratic terms in them. For example, a very successful folding model had the signs reversed on hydrophobic and some electrostatic interactions. It made no sense physically but it gave a better prediction than competing models, and it was hard to move away from because it ranked well in CASP.

dekhn 2y ago
Which model had the signs reversed? Yes, CASP was prone to getting stuck in local minima. I think the whole structure prediction field had become moribund.

throwawaymaths 2y ago

Refreshingly good. Bakers "early" (not really early, but earlier than AlphaFold) work (having humans with no background solve folds) really laid the groundwork to proving that heuristic methods were likely to outperform physical forcefield and ab initio/DFT methods for structure prediction. And AI structure prediction if nothing else is heuristic protein folding.

siver_john 2y ago

They had to put David Baker on here, his work on protein design if nothing else was ground breaking. I've expected him to win it at some point in a, it's not a matter of if but of when.

deleted 2y ago

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