binding affinity data for the co-crystals provided?

[linminhtoo]

Hi authors of the SAMPL challenges,

I chanced across this database serendipitously as I am looking for datasets that have co-crystal PDB structures along with corresponding binding affinity assay values.

I saw that you have a folder of 50+ co-crystal structures in https://github.com/samplchallenges/SAMPL7/tree/master/protein_ligand/stage-3-input-data/cocrystals

Is there corresponding binding affinity data for these as well? It would be perfect for my use-case!

Thank you

[davidlmobley]

No, there is not. @haroldgrosjean may be able to comment more but my understanding is that experimental limitations, such as issues with solubility, prevented affinity measurement.

[linminhtoo]

Ah I see, that's a shame... So am I right to say there's no binding or efficacy data of any kind? (even IC50)

Thanks for the response :)

[haroldgrosjean]

Hello! Indeed - we've tried to run ITC on those fragments without much success, unfortunately. The issues were mostly related to solubilities, the ITC devise being difficult and compounds processing (i.e compounds arriving in a past/ liquid instead of powders).

For the few binding events that we did observe (2 or 3), the crystals poses were really unstable when running MD simulations which make me believe that the binding mode resolved may not be the same as the one(s) that trigger the biophysical signal.

This data is not being use so I would be very happy to share it with you anyway.

If you're interested or would like to know more, please don't hesitate to email me at [email protected]

Bests,

Harold