Sequence Effect of Peptide-Based Materials on Delivering Interferon-α (IFN-α): A Molecular Dynamic Perspective

Area of Science:

• Biomaterials Science
• Molecular Biophysics
• Drug Delivery Systems

Background:

• Peptide-based biomaterials are promising for drug delivery due to biocompatibility and biodegradability.
• The microscopic roles of specific amino acids in peptide-protein interactions for delivery remain unclear.

Purpose of the Study:

• To investigate the sequence-dependent assembly behavior of peptides around interferon-alpha (IFN-α).
• To quantitatively characterize how peptide sequences affect the delivery of therapeutic proteins at a microscopic level.

Main Methods:

• Utilized all-atom molecular dynamics simulations to study peptide-IFN-α interactions.
• Analyzed peptide self-assembly, encapsulation efficiency, and interaction energies.

Main Results:

• Hydrophobic peptides aggregated without encapsulating IFN-α.
• Hydrophilic peptides phase-separated from IFN-α.
• Hybrid peptides (VPKEG) formed protective shells, enhancing IFN-α stability and stealth properties, balancing protection and release.
• Lysine (positive charge) enhanced binding affinity; Glutamate (negative charge) contributed to hydrophilicity.

Conclusions:

• Peptide sequence critically determines assembly and delivery behavior.
• Hybrid peptides with repeating hydrophobic and charged residues are suitable for therapeutic protein delivery in solution.
• Understanding amino acid contributions is key to designing effective peptide-based drug delivery systems.