Publication date: Jul 02, 2025
Protein-receptor interactions play a critical role in viral entry and pathogenesis. While ACE2 is the primary receptor for SARS-CoV, the role of DPP4 as potential coreceptor remains underexplored. This study investigates the binding mechanisms and dissociation dynamics of the SARS-CoV/DPP4, SARS-CoV/ACE2 and MERS-CoV/DPP4 complexes using molecular docking and molecular dynamics simulations. The SARS-CoV/DPP4 complex exhibited the highest free-energy barrier ( ), suggesting significant stability despite being energetically unfavorable. In contrast, the MERS-CoV/DPP4 complex, with the lowest free-energy barrier ( ), was the most likely to form and the least resistant to dissociation. The SARS-CoV/ACE2 complex demonstrated the highest , reflecting well-organized interfacial side chains that facilitate hydrogen bonding, yet its relatively low free-energy barrier and dissociation temperature made it prone to dissociation. These findings highlight an inverse relationship between electrostatic complementarity and protein-protein complex stability, where increased electrostatic complementarity correlates with reduced stability due to frustration from competing interactions. While DPP4 may serve as a coreceptor for SARS-CoV, its interaction is constrained by significant energy barriers, suggesting it may only occur under specific biological conditions or alternative binding pathways.
Open Access PDF
| Concepts | Keywords |
|---|---|
| Competing | ACE2 |
| Lowest | dissociation energy |
| Pathogenesis | DPP4 |
| Proteins | free energy |
| Viral | MERS‐CoV |
| molecular dynamics | |
| SARS‐CoV | |
| SMOG |