I routinely perform pulldowns in order to purify a protein of interest, and afterwards I digest linear nucleic acids attached to my bait protein using micrococcal nuclease (MNase). So far I have performed digestions after eluting my protein of interest from the resin, with satisfactory results.

I now plan to perform a in-resin MNase digestions, without previous elution of my target protein. Has anyone used MNase in-resin? I wonder how much the digestion efficiency could be affected by the resin itself, which can be critical in order to obtain reproducible results. Any tips regarding how to optimize the reaction?

Thanks.