5 ms·
Yes, Rosetta did monte carlo substitution of 9-mers, followed by a refinement phase with 3-mers. Plus a bunch of other stuff to generate more specific backbone
by timr 2y ago
Yes, Rosetta did monte carlo substitution of 9-mers, followed by a refinement phase with 3-mers. Plus a bunch of other stuff to generate more specific backbone "moves" in weird circumstances.
In order to create those fragment libraries, there was a step involving generation of multiple-sequence alignments, pruning the alignments, etc. Rosetta used sequence homology to generate structure. This wasn't a wild, untested theory.
- flobosg 2y ago> Rosetta used sequence homology Rosetta used remote sequence homology to generate the MSAs and find template fragments, which at the time was innovative. A similar strategy is employed for AlphaFold’s MSAs containing the evolutionary couplings.
- timr 2y agoYep. That's what I'm saying.
- dekhn 2y agoI don't know that I agree that fragment libraries use sequence homology. From my understanding of it, homology implies an actual evolutionary relationship. Wheras fragment libraries instead are agnostic and instead seem to be based on the idea that short fragments of non-related proteins can match up in sequence and structure space. Nobody looks at 3-mers and 9-mers in homology modelling; it's typically well over 25 amino acids long, and there is usually a plausible whole-domain (in the SCOP terminology). But, the protein field has always played loose with the term "homology".