I am trying to understand that without phosphomimics, will it be possible to design chemical compound that can displace phosphate (ATP or phosphopeptide) interaction. I looked into type1 kinase inhibitors (e.g, BRAF), they occupy at the adenine site only, and seems like they don’t compete with phosphate (of nucleotide). So, lets say if I have a protein which has a phosphosite with minimal hydrophobic cavity (bind at surface), will it be possible to design a non-phospho mimick inhibitor (combining H-bond donor/acceptor chemistry) for that site?
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