Protein-protein interactions (PPI) have emerged as valuable targets in medicinal chemistry due to their key roles in important biological processes. The modulation of PPI by small peptides offers an excellent opportunity to develop drugs against human diseases. Here, we exploited the knowledge of the binding interface of the IgG-protein G complex (PDB:1FCC) for designing peptides that can inhibit these complexes. Herein, we have designed several closely related peptides, and the comparison of results from experiments and computational studies indicated that all the peptides bind close to the expected binding site on IgG and the complexes are stable. A minimal sequence consisting of 11 amino acids (P5) with binding constants in the range of 100 nM was identified. We propose that the main affinity differences across the series of peptides arose from the presence of polar amino acid residues. Further, the molecular dynamic studies helped to understand the dynamic properties of complexes in terms of flexibility of residues and structural stability at the interface. The ability of P5 to compete with the protein G in recognizing IgG can help in the detection and purification of antibodies. Further, it can serve as a versatile tool for a better understanding of protein-protein interactions.
Keywords: Binding thermodynamics; Isothermal titration Calorimetry; Protein-peptide interaction.
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