Insights into Structure and Aggregation Behavior of Elastin-like Polypeptide Coacervates: All-Atom Molecular Dynamics...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Computational Biophysics

Background:

• Stimuli-responsive elastin-like polypeptides (ELPs) are utilized in diverse applications.
• The lower critical solution temperature (LCST) behavior of ELPs involves complex aggregation mechanisms.
• Understanding ELP coacervate structure and dynamics is crucial for optimizing their use.

Purpose of the Study:

• To investigate the molecular mechanisms behind ELP aggregation and coacervate formation.
• To elucidate the sequence-dependent structural differences between ELP aggregates.
• To provide insights into the behavior of individual ELP chains during aggregation.

Main Methods:

• All-atom molecular dynamics simulations were employed.
• Simulations were conducted on 27 90-mer ELPs in explicit water at 350 K.
• Two specific ELP sequences, poly(VGPVG)18 and poly(VPGVG)18, were analyzed.

Main Results:

• Simulations revealed differences in surface hydrophobicity between poly(VGPVG) and poly(VPGVG) aggregates.
• Significant changes in torsion angles and secondary structural motifs were observed during aggregation.
• The structure of individual polypeptides differs markedly between the dissolved and aggregated states.
• Aggregation is driven by peptide-peptide interactions, with consistent average peptide hydration.
• ELP coacervates lack a hydrophobic core and retain substantial water content.

Conclusions:

• ELP aggregation is sequence-dependent, influencing coacervate structure.
• The aggregation process involves structural transitions and peptide-peptide interactions.
• ELP coacervates are hydrated structures, challenging the notion of a purely hydrophobic core.