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nrbennet / dl_binder_design

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In lab experiment, binding affinity is pretty strong, but pae_interaction is only around 28 #82

Open Huilin-Li opened 3 months ago

Huilin-Li commented 3 months ago

So, I have an example protein A that is very similar to my protein B I aim to study. The protein A has a binder A-binder, and I use A-binder as a scaffold to design my binder B-binder to my protein B.

As I learned here, at the last step, I will use af2_initial_guess/predict.py to assess designed binders and pick binders whose pae_interaction<10 .

However, pae_interaction~=28 between protein A and A-binder. I feel confused about it a lot, because its binding affinity is very strong in lab experiment.

I worked very hard to think of how to improve pae_interaction below 10. Unfortunately, over 95% pae_interaction is around 26~28. Should I still work hard to look for pae_interaction<10 ?

I don't understand these two scenarios: 1) why pae_interaction is bad, but binding affinity is very strong in lab experiment? 2) Is pae_interaction<10 very important? Is there any other criteria I should to consider when I assess my designed binders?

Thanks a lot!!!

Jiny-Wang commented 2 months ago

hi, I have also encountered this problem and not seen a reasonable explanation so far.

I think the calculation of pae_interaction is related to the size of binder (mine is about 70) and the interface area. How many aa does your B-binder have?

At the moment it looks like: "pae_interaction < 10 is a good predictor of a binder working experimentally", but if your lab experiment are good, other evaluation scores may be needed.