Bereiche | Tage | Auswahl | Suche | Aktualisierungen | Downloads | Hilfe

BP: Fachverband Biologische Physik

BP 20: Protein Structure and Dynamics

BP 20.5: Vortrag

Mittwoch, 11. März 2026, 16:30–16:45, BAR/0106

Microscopic Insights into the Solvation of Stapled Peptides A Case Study of p53-MDM2 — Vikram Gaikwad, •Asha Rani Choudhury, and Rajarshi Chakrabarti — Indian Institute of Technology Bombay, Mumbai, India

Water often termed the universal solvent, plays a vital role in numerous biomolecular processes, including protein-protein interactions. One such critical complex is p53-MDM2, which is central to cellular regulation. Inhibiting the p53-MDM2 interaction remains a therapeutic challenge, and stapled peptides have emerged as promising candidates in this context.The stapled peptides are peptidomimetics in which the side chains of two suitably positioned amino acids are covalently linked using an appropriate chemical moiety. In this study, we investigate the role of water in the binding of stapled p53 peptides to MDM2 using molecular dynamics simulations. Our aim is to understand how variations in the chemical nature and stapling position of the hydrocarbon cross-linker influence the behavior of water molecules surrounding the p53 peptide. Using rigorous entropy calculations, we rationalize the enhanced binding affinity of stapled p53 peptides compared to that of their unstapled counterparts from a solvent-centric perspective. Specifically, the entropy gain of water molecules around the stapled peptides, combined with the conformational entropy loss of the peptide, contributes favorably to binding. These findings offer valuable insights into the rational design of stapled peptides and support the development of improved therapeutic inhibitors targeting the p53-MDM2 interaction.

Keywords: Protein-protein interaction; Stapled p53 Peptide; Hydrocarbon cross-linker; Water dynamics; Entropy