Designing A Ligand-Like Protein For Blocking of Tim-3

Background and aim: t cell immunoglobulin and mucin-domain containing-3 (tim-3) is a type i transmembrane protein that plays a key role in regulating innate and adaptive immune responses in infections, autoimmune diseases, and tumors by binding to its ligands especially (ceacam1) and inhibiting th1 responses and the expression of cytokines such as tnf and inf-γ. therefore, this receptor and its ligand are increasingly being considered as a target for numerous therapeutics that are under clinical development. in this study, the extracellular region of ceacam1 was mutated with bioinformatics tools to increase its binding affinity for its receptor (tim-3). as this engineered protein will bind to tim-3, natural ligand (ceacam1) cannot bind to the tim-3 in the cell membrane. as a result, tim-3 will not activate and t-cell will not be inhibited so the progression of autoimmune and inflammatory diseases and cancer will stop.methods: the ceacam1 sequence was mutated by the r software. interaction of each mutant to tim-3 was investigated by haddock server and the binding energy was calculated by foldx software.results: among the 100 mutants of ceacam1, the mutant containing the y34k point mutation was the best mutant because it had the lowest binding energy and highest binding affinity relative to natural ceacam1.conclusion: this engineered protein had lower binding energy than wild-type protein, so it could bind more strongly to tim-3 protein.