(516d) Assembly of Short Amphiphilic Peptoids into Nanohelices with Controllable Supramolecular Chirality: Insights from Computational Simulation and Theoretical Analysis

Computational modeling and theoretical analysis are pivotal for gaining a deep understanding of the structures and functions essential for the rational design of synthetic biomaterials that mimic natural counterparts. In this work, we present the formation of a series of nanohelices derived from a well-established class of peptide-mimetics known as peptoids (poly-N-substituted glycines). These peptoid nanohelices are designed to mimic the helical protein assemblies crucial in biological systems. By integrating experimental mechanistic studies, molecular dynamics simulations, and theoretical analysis, we demonstrate that the structures of nanohelices and their supramolecular chirality can be precisely controlled through side-chain chemistry. Molecular dynamics simulations unveil the thermodynamically favorable ordered packing of these amphiphilic peptoids and the transition process from flat sheets to twisted nanofibrils. Furthermore, we have developed a phenomenological free energy model to elucidate the self-assembly of the twisted ribbons. This model provides insights into the twisted ribbon geometry as a function of solvent conditions and intermolecular attractions. Our research indicates that amphiphilic peptoids minimize the exposure of hydrophobic domains by adopting a twisted helical conformation, underscoring the significant roles of both polar and hydrophobic domains in nanohelix formation. The ability to precisely control the structural organization of sequence-defined peptoids and their supramolecular chirality of their assemblies opens the door to a system suitable to reveal how molecular interactions between fundamental chemical moieties control the arrangement, packing, and assembly of biomacromolecules and inorganic particles, generating a wide range of protein-like, functional nanomaterials as nanocarriers for drug delivery, as artificial enzymes for catalytic reactions, and as scaffolds for biomimetic mineralization. Overall, our findings establish a foundation for designing and synthesizing chiral functional materials using sequence-defined synthetic polymers.