Proposal for the binding mode of the 23-mer inhibitory peptide to myostatin

Inhibition of myostatin is a promising strategy for the treatment of amyotrophic disorders. Previously, we identified a minimum 23-mer peptide spanning positions 21-43 of a mouse myostatin precursor-derived pro domain and identified the nine key residues for effective myostatin inhibition through Ala scanning. We also reported the 23-mer peptides that show the propensity to form an alpha-helical structure around positions 32-36. Here, based on these findings, we conducted a docking simulation of a peptide-myostatin interaction. The results showed that by alpha-helix restraint docking of the 30-41 main chain, we obtained a proposed binding mode in which all nine of the key residues interact with myostatin. By analyzing the binding mode of four proposed docking models, we identified six of the myostatin residues that play an important role in the interaction with the peptide. This result provides a valuable insight into the relationship between myostatin and peptide interaction sites and may help in the design of future inhibitors.

Automated summary

Inhibition of myostatin is a promising approach for treating muscle wasting disorders. Through docking simulations of a 23-mer peptide with myostatin, key residues and interaction sites were identified, providing insights for future inhibitor design.