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

• DOI: 10.1021/acs.langmuir.1c02515
• Publication Date: 2022-01-05T22:10:01Z
• Authors: Yuting Liu; Guoliang Zhu; Zhuanglin Shen; Yantao Chen
• Keywords: Sequence (biology)

Peptide-based biomaterials exhibit great potentials in developing drug delivery platforms due to their biocompatibility and biodegradability beyond poly(ethylene glycol). How different amino acids peptides used for play roles is still unclear at the microscopic level. This work compared assembly behaviors of a series around interferon-α (IFN-α). Through all-atom molecular simulations, sequence effect on delivering was quantitively characterized. The hydrophobic elastin-like peptide (VPGAG)n preferred self-aggregate into dense clusters, rather than encapsulate IFN-α. hydrophilic zwitterionic with repeating unit "KE" tended phase-separate from IFN-α mixture. In contrast, hybrid sequence, i.e., (VPKEG)n, exhibited highest contact preference, formed protective shell endowed better thermal stability stealth property achieved subtle balance between protecting subsequent releasing. Further energy decomposition analysis revealed that positively charged Lys contributed most binding affinity while negatively Glu peptide-based materials. summary, this article reveals why composed residues could be potential choice therapeutic proteins form solution.