Interfaces in the HVEM:LIGHT:BTLA:CD160 complex and schema of design process. Three rows refer to binary complexes of HVEM with LIGHT, BTLA, and CD160m, respectively. (A) Crystal structures of complexes of LIGHT, CD160, and BTLA with HVEM. (B) Corresponding cartoon representation: yellow eclipse represents cysteine rich domains of HVEM and rectangle-like shape represent ligand monomers. (C) Interface residues from both proteins are represented using circles within the white area and their corresponding interactions are shown in black line. (D) rs-pharmacophore residue preference as calculated by ProtLID (E) Rs-pharmacophore guided design of HVEM interface. (F) Effective mutations for modulating HVEM specificity in six different ways.