Polymorphic Self-Assembly of 4-Imidazolidinone-Fused Asymmetric Cyclic Peptides

The self-assembly of asymmetric cyclic peptides offers considerable promise for the design of functional nanomaterials. In this study, we systematically investigate the concentration-dependent self-assembly of 4-imidazolidinone-fused asymmetric cyclic peptide (ACP) molecules using dissipative particle dynamics (DPD) simulations. Our findings reveal the evolution of self-assembled structures determined by ACP molar percentage: At low molar percentages (3-6%), ACP molecules assemble into core-shell ellipsoidal nanoparticles; at intermediate concentrations (7-10%), irregular quasi-spherical clusters emerge; and at higher molar percentages (11-20%), nanorod structures develop. Notably, at 11% molar ratio, the geometric asymmetry imparted by the 4-imidazolidone heterocycle drives the hydrophobic beads to spontaneously assemble into a double-helical configuration. This finding aligns with experimentally observed twisted morphologies and demonstrates the direct translation of molecular-scale asymmetry into a well-defined mesoscopic structure. Mechanistic analysis indicates that hydrophobic bead-hydrophilic bead interactions serve as the primary driving force throughout the self-assembly process, with their influence strengthening as ACP concentration increases. This study elucidates the mesoscale mechanism underlying the polymorphic self-assembly of ACP molecules, providing a theoretical foundation and computational framework for the rational design of peptide-based nanomaterials.