Next, we set out to modify the standard RaPID protocol to bias it towards the selection of photocrosslinking ligands. To retain only covalently crosslinked peptides during affinity panning, we envisaged replacing the standard wash buffers with wash buffers that would denature the target protein (Figure ). This should allow removal of all non-covalently bound peptides, after which the crosslinked protein-peptide conjugates could be eluted from the beads by boiling. The DNA associated with the crosslinking peptides could then be isolated by PCR and carried forward to the next round.