Post by CrystalsFirst

𝐅𝐫𝐨𝐦 “𝐞𝐦𝐩𝐭𝐲” 𝐜𝐫𝐲𝐬𝐭𝐚𝐥 𝐬𝐭𝐫𝐮𝐜𝐭𝐮𝐫𝐞𝐬 𝐭𝐨 𝐬𝐨𝐥𝐯𝐞𝐝 𝐜𝐨-𝐬𝐭𝐫𝐮𝐜𝐭𝐮𝐫𝐞𝐬 Covalent campaigns don’t usually stall because the compounds are not active. They stall because the co-structure never arrives or the resolution is not sufficient to resolve the binding mode. In our example, protein crystals of a human reductase are formed under acidic conditions, the  cysteine is protonated and not reactive. Changing the environment of crystals towards higher pH for soaking dissolves crystals in conventional set ups. In this case, SmartSoak was applied and a high-throughput soaking system was established at a pH which facilitates cysteine reactivity. The ligands appeared in the active site indicating a novel mode of action at 1.3 Å resolution. Our patented SmartSoak technology delivers co-structures reliably and with short turnover cycles. It has been successfully applied for covalent and non-covalent campaigns, for fragments, leads, drug candidates, peptides and macrocycles.