The MP targets, by engineering a small number of single point mutations outside of the ligand-binding pocket, retains their organized conformations and are more robust than the corresponding wild-type proteins. These MP targets are well subjected to SBDD of chemical entities. We also present MP antigens in different physiological states through the combination of mutational engineering and liposomes and nanodisc reconstitution, thus allowing for the discovery of a diverse panel of functional antibodies targeting different states of MP antigens.