An <i>in-silico</i> analysis of the interaction between selected honey bee venom peptides and the murine MHC-hMOG _37–46 complex for investigating potential therapeutic approaches in multiple sclerosis

The cellular immune responses associated with multiple sclerosis are triggered when T-lymphocyte receptors interact with the MOG epitope-MHC complex. By inhibiting the formation of this harmful trimeric complex (MHC-epitope-TCR), it is possible to alleviate the symptoms of MS. In this research, one of the human neuroantigenic epitopes (hMOG_37-46) involved in MS was bound to mouse MHC, forming a dimer complex (mMHC-hMOG). Subsequently, 12 peptides derived from honey bee venom were selected. Each peptide underwent a separate 100 ns molecular dynamics (MD) simulation before being docked into the binding cleft of the dimer complex, facilitating the identification of the most favorable complex. These trimer complexes were then subjected to an additional 100 ns MD simulation, and the binding free energy for each bee peptide to the dimer complex was computed using the MM/PBSA and quasi-harmonic methods. The findings indicated that Secapin 53-77 (YIIDVPPRCPPGSKFIKNRCRVIVP) demonstrated a greater binding affinity to the dimer complex. An examination of the binding site for this peptide within the dimer complex revealed a close similarity to the binding site of MHC with TCR, suggesting that this bee peptide can effectively obstruct the interaction between the mMHC-hMOG complex and TCR, thus preventing the onset of MS-related reactions. Also, another MD simulation showed that this peptide can bind to the complex human MHC-human MOG properly. Furthermore, based on the simulation results, a novel peptide (YIIKVHHRCHHGSKVIKNRCRVIVH) was designed, which also exhibited favorable interactions with the mMHC-hMOG complex. Finally, the residence times of these two peptides were determined through RAMD simulation.