Protein-protein interactions play a role in practically every biological process. The design of novel protein-protein interactions will improve our understanding of the biophysical parameters that drive molecular recognition and self-assembly in these biologically critical processes. Additionally, increased knowledge in the design and prediction of protein-protein interactions will potentially improve the discovery and design of new therapeutics. In a previous project, the monomeric β1 domain of streptococcal protein G (Gβ1) was computationally docked to itself in an antiparallel orientation. With the goal of producing a heterodimer in the docked orientation, the amino acid sequence at the docked interface was optimized by computational mutagenesis to produce a pair of proteins that form a heterodimer in the docked orientation. This computational design process resulted in a pair of proteins that are referred to as Monomer A and Monomer B. These two proteins were expressed, purified and characterized. The two computationally designed proteins were found to interact with each other as designed, however with a relatively low affinity. The objective of this project is to redesign the interface between Monomer A and Monomer B to obtain a pair of proteins that form a heterodimer with increased binding affinity. To this end we have taken two approaches. First, oppositely charged amino acids were added to the N- and C-termini of each monomer with the goal of strengthening the interaction by the addition of favorable electrostatic interactions. Next, metal coordination sites were engineered into the two monomers with the goal of increasing the affinity by cross-monomer coordination with metal ion(s) such as Zn(II) or Ni(II). The designed variants were expressed, purified and analyzed by size exclusion chromatography and an in vivo screening method (GFP fragment reassembly screen). While this project did not achieve the initial goal of producing a heterodimer complex with increased affinity over the computationally designed MonomerA/MonomerB complex, we did find that three of the Monomer A variants that were designed with metal coordination sites form homo-complexes in the presence of Zn(II), yet remain monomers in the absence of Zn(II). 2D [¹H, ¹⁵N] HSQC NMR spectra were collected for each of these three proteins in the presence and absence of Zn(II). Peak perturbation analysis of the spectra provided further evidence for zinc-induced complex formation.