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As it's a 'ShowHN' - we've only had the software public for a short time. Biology takes a while, so many of our clients who have used the software have chosen
by jfarlow 9y ago
As it's a 'ShowHN' - we've only had the software public for a short time. Biology takes a while, so many of our clients who have used the software have chosen to not yet make their designs public - they're still working with them.
What we can do is reverse engineer already published data into our system to see how it would work. If you're logged in you can see a synthetic Knoevenagel Catalyst like KN.1: https://serotiny.bio/pinecone/part/11291 https://serotiny.bio/pinecone/part/11291
or the Retroaldolase RA95.5-8: https://serotiny.bio/pinecone/part/11290 https://serotiny.bio/pinecone/part/11290
And from that page you can see the mutations that were made to create that new enzyme, as well as trace the history of the synthetic design from its current sequence all the way back to its wild-type ancestor through years of research.
Our background is not in computational design of proteins from their atomic structure (like Rosetta). We enable someone who does have that expertise - who has such a design in mind, to actually go about producing their libraries, getting the material delivered, evaluating the effectiveness of what they've produced, and sharing that information with their colleagues in a straightforward and actionable way. And if they're picking variants by a screen or directed evolution, Pinecone would be useful in describing the results of the screen in order to either move forward, or put the results to work.
Similarly, some of the fluorophores have great 'histories' to them - and with our software you can see how various fluorophores were designed, where they came from, and how they've been used. See Dronpa: https://serotiny.bio/pinecone/part/9036 https://serotiny.bio/pinecone/part/9036 or some of the pH-sensitive fluorophores like ArcLight: https://serotiny.bio/pinecone/part/10533 https://serotiny.bio/pinecone/part/10533
We'd like to think this enables a more straightforward 'porting' of existing designs into new scaffolds - if the mutations to GFP made it pH-sensitive, similar mutations to YFP will likely make it pH-sensitive. Swap the fluorophore entirely, or pull in a natural variant of Cas9 and likely the same sites that produced a nickase from spCas9 will work on other cas9 constructs.