Characterization of suramin binding sites on the human group IIA secreted phospholipase A2 by site-directed mutagenesis and molecular dynamics simulation

► The polyanion suramin is a human GIIA phospholipase A2 (hsPLA2GIIA) inhibitor. ► Single cationic residue mutants show increased or decreased suramin affinity. ► Altered suramin affinities correlate with intermolecular potential energy (IPE). ► Mutagenesis alters the conformation of the bound suramin to optimize the IPE. ► Molecules based on suramin can be used as novel hsPLA2GIIA inhibitors.