First, we’d like to thank all our contributors who have supported and continue to contribute to our scientific projects through Rosetta@home. We want to update you on the status of Rosetta@home projects and our future plans.

With the advancement of AI models like AlphaFold and RosettaFold for protein structure predictions, Rosetta@home has been less used for this purpose. However, researchers are now utilizing Rosetta@home for small molecule and peptide designs, where even the current state-of-the-art AI models struggle due to limitations in generalizability to novel small molecules and non-canonical peptides.

Recently, we have developed a virtual screening protocol in Rosetta, named RosettaVS, for small molecule drug discovery. This work has been published in Nature Communications (https://doi.org/10.1038/s41467-024-52061-7), demonstrating that RosettaVS is one of the best physics-based virtual screening protocols. Combined with deep learning techniques, it can effectively screen multi-billion compound libraries and discover novel compounds for pharmaceutical targets.

While deep learning models like AlphaFold and RosettaFold can predict canonical peptide structures, they cannot handle peptides with non-canonical amino acids or mixed chirality. The physics-based force field in Rosetta has specialized terms to simulate these amino acids. Rosetta will be used to sample hundreds of thousands of different conformations of the designed peptide to validate the structure.

Looking ahead, Rosetta@home will be an invaluable platform for large-scale virtual screening and peptide simulations for drug discovery. We plan to launch more virtual screening jobs and peptide simulations on Rosetta@home in the near future.

Thank you!

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It would be good if you could fix the problem with the security certificates on the download servers as many more people would then be able to contribute to doing work for Rosetta if they were able to download Tasks without having to edit their hosts file to make it possible.
It's been an issue for almost 5 months now (and the boinc-process host going down every week for a couple of days has been an issue for almost 12 months now).


Oh, and an update on the status of Ralph would be nice- no stats & broken project settings since Sept of last year. Along with no further work on the new application.
Making use of GPUs would result in a massive boost to your available compute resources, even more than fixing the download server issue (and doing both would boost them even more).

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Grant
Darwin NT

I'm almost crying after all this time from the last news!
As said Grant (SSSF), a gpu client is welcome

c'mon guys, let's do science!!

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It would be good if you could fix the problem with the security certificates on the download servers as many more people would then be able to contribute
to doing work for Rosetta if they were able to download Tasks without having to edit their hosts file to make it possible.
It's been an issue for almost 5 months now (and the boinc-process host going down every week for a couple of days has been an issue for almost 12 months now)

This is true and significant.
There are many willing users unable to work for Rosetta simply due to the expiry of security certificates - significant throughput is being lost every day - the most urgent issue.

Second biggest issue seems to be the incorrect setting of default runtimes to 4hrs on tasks running through Rosetta Beta 6.06 - instead of 8hrs

Third biggest issue is the daily cleanup job that awards credit to tasks with Validation failures (without Compute errors). This job hasn't run for a year or more

Fourth issue is the boinc-process server going down every Wednesday (no task validation / assimiliation) and only returning every Friday for the last 6(?) weeks (more an annoyance than a problem, but its regularity indicates a failure that's easily fixable)

Solve these 4 problems for a significant bump in both pace and throughput of tasks you say Rosettafold & Alphafold can't handle, but which we can gladly support.
Even if it takes a whole day to fix these issues (it won't) it'll be repaid 10-fold - supporting us to support you back (also shutting us all up by keeping us happy). Win - win.

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