RosettaCommons
RFD3
Dear Developers,
Thank you for open-sourcing such a powerful tool!
When I use RFD3 for protein–small-molecule design, I set the hydrogen-bond donors and acceptors, but it seems to have no effect—the generated designs still do not form hydrogen bonds. Could you please help me understand why this happens?
Thank you very much for your assistance!
Can you provide more details about the settings you were using in you calculation? Do you have hbplus installed and your environment paths set correctly? There are instructions for this in the RFD3 README and in the na_binder_design examples.
Hi ZhuLvs, thanks for your kind words!
To rachels point you can find the hydrogen bonds made in the metrics json if hbplus is installed - RFD3 won't get the hydrogen bonds right every time. You can increase the general propensity toward the condition using classifier free guidance - can be enabled from the cli using inference_sampler.use_classifier_free_guidance=True - in the paper we show this can help on some cases (figure 2d), so would give that a shot and at different scales (inference_sampler.cfg_scale>1.5) if still no budge!
Hi ZhuLvs, thanks for your kind words!
To rachels point you can find the hydrogen bonds made in the metrics json if hbplus is installed - RFD3 won't get the hydrogen bonds right every time. You can increase the general propensity toward the condition using classifier free guidance - can be enabled from the cli using
inference_sampler.use_classifier_free_guidance=True- in the paper we show this can help on some cases (figure 2d), so would give that a shot and at different scales (inference_sampler.cfg_scale>1.5) if still no budge!
Thank you for your help. I installed hbplus and specified the environment variables, but I ultimately got a NameError: name 'strip_X' is not defined. Does this mean hydrogen bonding is not applicable in protein-ligand design?
Ah there was a missing import, have fixed this on this commit: https://github.com/RosettaCommons/foundry/commit/73d43c50e1943fcd34859a9236b5a0594608496d