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> What is different about the new AlphaFold3 model compared to AlphaFold2? > AlphaFold3 can predict many biomolecules in addition to proteins. AlphaFold2 predi
by renonce 2y ago
> What is different about the new AlphaFold3 model compared to AlphaFold2?
> AlphaFold3 can predict many biomolecules in addition to proteins. AlphaFold2 predicts structures of proteins and protein-protein complexes. AlphaFold3 can generate predictions containing proteins, DNA, RNA, ions,ligands, and chemical modifications. The new model also improves the protein complex modelling accuracy. Please refer to our paper for more information on performance improvements.
AlphaFold 2 generally produces looping “ribbon-like” predictions for disordered regions. AlphaFold3 also does this, but will occasionally output segments with secondary structure within disordered regions instead, mostly spurious alpha helices with very low confidence (pLDDT) and inconsistent position across predictions.
So the criticism towards AlphaFold 2 will likely still apply? For example, it’s more accurate for predicting structures similar to existing ones, and fails at novel patterns?
- deleted 2y ago[deleted]
- dekhn 2y agoI am not aware of anybody currently criticiszing AF2's abilities outside of its training set. In fact the most recent papers (written by crystallographers) they are mostly arguing about atomic-level details of side chains at this point.
- COGlory 2y ago>So the criticism towards AlphaFold 2 will likely still apply? For example, it’s more accurate for predicting structures similar to existing ones, and fails at novel patterns? Yes, and there is simply no way to bridge that gap with this technique. We can make it better and better at pattern matching, but it is not going to predict novel folds.
- dekhn 2y agoalphafold has been shown to accurately predict some novel folds. The technique doesn't entirely depend on whole-domain homology.
- flobosg 2y ago> but it is not going to predict novel folds https://www.nature.com/articles/s42003-022-03357-1 https://www.nature.com/articles/s42003-022-03357-1
- rolph 2y agoproblem is biomolecules, are "chaperoned" to fold properly, only specific regions such as, alpha helix, or beta pleatedsheet will fold de novo. Chaperone (protein) https://en.wikipedia.org/wiki/Chaperone_(protein) https://en.wikipedia.org/wiki/Chaperone_(protein)
- staticautomatic 2y agoIn principle couldn’t we just incorporate knowledge about chaperones into the model?
- flobosg 2y agoIn a way it is already incorporated. Broadly speaking, chaperones function by restricting the available conformational sampling space for the protein to fold. Some researchers even consider the ribosome as a chaperone of sorts for the nascent protein chain it synthetizes. Protein structure prediction methods do the same: they find ways of restricting the conformational space to explore, in hopes of finding the global minimum-energy conformation representing the native structure of the protein.
- staticautomatic 2y agoThen it’s not clear to me exactly why should chaperones be a problem, though I get the gist intuitively
- rolph 2y agoif you want a protien or any other bio molecule to fold properly, a chaperone system must be either designed or elucidated. the primary sequence is not the only consideration for proper folding. chaperones allow higher energy folding events to occur and be maintained until subsequent modification stabilizes high energy structural motif. chaperones also enforce an A before B before C regime of folding so that the sequence doesnt just crumple up according to energy of hydrostatic interactions