More Protein Folding Progress – What’s It Mean?

Re:More Protein Folding Progress – What’s It Mean? by dnautics on Monday July 26, 2021 @03:59PM (#27964586)

One crazy idea I have is to run some very crude ab-initio QM or DFT stuff starting with folded proteins, and gradually running the temperature higher until it unfolds. Then amass a dataset of protein structures + positional delta vectors. Then time-reverse the dataset (flip the sign on those vectors). Then train a 3d convolutional NN on the reverse-melting curve to obtain heuristic rules for folding in whatever universe the shitty physics engine represents.

Then it doesn't matter if the QM simulation is very crude and deeply flawed, so long as it gets to the right answer at the end.

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Re:More Protein Folding Progress – What’s It Mean? by dekhn on Monday July 26, 2021 @04:14PM (#27964809)

IIUC the folding and unfolding pathways of a protein are not time reversed wrt each other.

But you would still enjoy reading this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC17732/ the work in this paper led to folding@home because vijay couldn't get enough computer time to run his simulations

if you really had a lot of computer time to waste, you could imagine doing simulations where you titired in or out some guanadinum chloride and inspected how disrupting h-bonds (versus hydrophobic collapse) contributes. Chaotropes are better than temperature for probing unfolding.

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Re:More Protein Folding Progress – What’s It Mean? by dnautics on Monday July 26, 2021 @10:12PM (#27967846)

> IIUC the folding and unfolding pathways of a protein are not time reversed wrt each other.

That's more or less correct, but in my proposal, we are not modeling the folding pathway of a protein. One way to think of it: we would be modelling the reverse unfolding pathway of a protein in a universe with different (simpler) physics than ours, physics in which (hopefully) the time reversed unfolding pathway yields the correctly folded protein in OUR universe.

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Re:More Protein Folding Progress – What’s It Mean? by d110af5ccf on Tuesday July 27, 2021 @03:15AM (#27969536)

Your description kind of reminds me of the 2018 World Models publication. Are you familiar with that work and/or am I off base? (https://worldmodels.github.io/) (https://arxiv.org/abs/1803.10122)

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Re:More Protein Folding Progress – What’s It Mean? by dnautics on Tuesday July 27, 2021 @11:24AM (#27973561)

Off base. I'm using universes as a florid description of the fact that our QM models are crap but they might be useful of the laws of physics were different.

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