Effect of Stapling on the Thermodynamics of mdm2–p53 Binding

Protein–protein interaction (PPI) is one of the key regulatory features driving biomolecular processes and hence targeted for designing therapeutics against diseases. Small peptides are a new emerging class owing to their high specificity low toxicity. For achieving efficient targeting PPI, amino acid side chains often stapled together, resulting in rigidification these peptides. Exploring scope demands comprehensive understanding working principle. In this work, two p53 have been considered delineate binding mechanism with mdm2 using computational approaches. The addition stapling agent protects secondary structure even case thermal chemical denaturation. Although introduction increases hydrophobicity peptide, enthalpic stabilization decreases. This overcome by lowering entropic penalty, overall affinity improves. mechanistic insights into benefit peptide can be adopted further improvement therapeutics.