4 ms·

> Didn't the challenge include predicting previously unseen/unsolved proteins? All protein sequences in the competition lacked a published solved structure, bu

> Didn't the challenge include predicting previously unseen/unsolved proteins? All protein sequences in the competition lacked a published solved structure, but they had enough effective (remotely) homologous sequences to predict coevolution-derived interresidue distances and contacts. All those sequences were already present in databases and therefore within the known protein universe. > Based on that, I would wager that what DeepFold learned is an evolutionary "language" that maps out a large useful subset of the entire possibility space. This might be true, depending on how “foldable” the unexplored space is. A reverse DeepFold would give some clues on that. > Natural evolution tends build upon previous successes so it seems probable evolution has mapped out a fairly useful "language" of patterns for useful protein shapes This is already known. The structural and functional diversity we see in existing proteins originated from a relatively limited repertoire of conserved protein domain folds, or even subdomain-sized fragments in some cases. > Either way, I'm excited to see who comes up with the first custom protein(s) to catalyze industrial processes! Same here! Especially since the de novo design of enzymes has been progressing slowly but steadily.

elcritch 6y ago
> but they had enough effective (remotely) homologous sequences to predict coevolution-derived interresidue distances and contacts. Ah, I see what you're saying a bit better. Makes more sense to how the the possible "design" space for novel proteins could be limited. Designing novel active sites could be especially tricky, more than it'd seem at first glance. A folded structure that'd effectively transfer electrons from one target species to another in a catalyzer protein could likely be outside the explored "vocabulary" of extant proteins as it'd require specialized pathways and precise positioning. Chlorophyll is pretty unchanged in evolution as I understand it.Thanks, interesting background! I'll keep an eye out for the de novo design algorithms.

elcritch 6y ago

> but they had enough effective (remotely) homologous sequences to predict coevolution-derived interresidue distances and contacts. Ah, I see what you're saying a bit better. Makes more sense to how the the possible "design" space for novel proteins could be limited. Designing novel active sites could be especially tricky, more than it'd seem at first glance. A folded structure that'd effectively transfer electrons from one target species to another in a catalyzer protein could likely be outside the explored "vocabulary" of extant proteins as it'd require specialized pathways and precise positioning. Chlorophyll is pretty unchanged in evolution as I understand it.Thanks, interesting background! I'll keep an eye out for the de novo design algorithms.