A combined experimental and computational approach reveals how aromatic peptide amphiphiles self-assemble to form ion-conducting nanohelices

Abstract

Salt-triggered conversion of nanoribbons into nanohelices was studied experimentally and computationally, revealing unexpectedly high ionic conductivity in these self-assembled nanomaterials.

Development, Validation, and Applications of Nonbonded Interaction Parameters between Coarse-Grained Amino Acid and Water Models

“…To test the applicability of the new optimized nonbonded parameters between amino acids and water, we performed the self-assembly of two PAs in water. Specifically, we selected two different PAs, namely, c16-AHL3K3-CO2H and FA32, that form fibers and micelles, respectively, in the presence of water. ,− In general, interactions between water and the hydrophilic and hydrophobic portions of the PAs are known to play an important role in the self-assembly process.…”

“…Processes such as self-assembly and folding/unfolding of proteins occur at the length and time scales of nanometers and microseconds, respectively. − Although the development of novel experimental methods has enabled accurate characterization of these self-assembled nanostructures, following the self-assembly pathway still remains challenging . Consequently, during the past decades, computational methods such as coarse-grained (CG) molecular dynamics (MD) simulations have drawn a lot of attention to provide in-depth insights into the mechanisms governing these molecular processes. ,,− However, the accuracy of these results depends significantly on the intra- and intermolecular interaction parameters between the CG beads and the solvent, defined by the force-field (FF). − Several research groups have developed CG models of amino acids, but most of these studies have used implicit water models, which makes it impossible to understand the structure of the solvent at the solute–solvent interfaces . Of the few models that can be used with explicit water beads, − the Martini FF, one of the most common models for protein CG MD simulations, is also known to have limitations like its inability to predict the Gibbs hydration free energy of CG molecules. ,− In addition, these models may underestimate the characteristics of self-assembled structures and may not be suitable to study elastin-like peptides that exhibit a lower critical solution temperature (LCST). ,, Thus, it is important to develop FF parameters to accurately model the interactions between amino acids and water.…”

“…Among the hundreds of amino acids found in nature, 20 amino acids make up all proteins in the human body. − The interactions of these amino acids with water are instrumental for accurate protein folding and maintaining the stability of these complex structures, thus influencing their overall functions. − For example, hydrophobic amino acids, when clustered in the interior of cytoplasmic proteins, may form ligand-binding pockets essential for signaling and enzyme catalysis. − Similarly, hydrophilic amino acids in the interiors of transmembrane proteins are essential for extracellular transport of water and ions, thus maintaining cellular homeostasis. , Moreover, interactions between amino acids and water are advantageous in creating novel peptide-based (macro)­molecules including artificial peptide polymers and peptide amphiphiles with unique properties and functionalities. − A combination of both hydrophilic and hydrophobic amino acids in elastin-like polypeptides (ELPs)a class of artificial peptide polymersand their interactions with water is believed to be responsible for their lower critical solution temperature (LCST) behavior. , In the case of peptide amphiphiles (PAs), the sequence of peptides, their concentration, and interactions with water results in self-assembled structures, such as micelles, fibers, rods, and many more, regulated by environmental conditions such as temperature and pH. − Several experimental and computational studies have shown the self-assembly of PAs into micelles and consequently fibers, having micron-sized lengths and nanometer-sized diameters (1–10 nm). ,,− Moreover, self-assembled structures of PAs have shown great promise in biomedical applications like bone regeneration, tissue engineering, gene and drug release, regenerative medicine, etc. ,, Hence, understanding amino acid–water interactions is essential in order to gain insight into the conformations and function of many biomolecules in aqueous solutions.…”

The Martini Model in Materials Science

“…[ 229 ] Many groups have explored their self‐assembly process by leveraging the Martini model. [ 230–252 ] Besides allowing simulation of the self‐assembly and growth, Martini is also particularly suited for high‐throughput applications. An example of such a high‐throughput application in the area of peptide‐based supramolecular materials is the work of Frederix et al.…”

Effects of Cell-Adhesive Ligand Presentation on Pentapeptide Supramolecular Assembly and Gelation: Simulations and Experiments

“…While various methods of simulation aid in the design of soft materials, MD has proven to be effective for studying peptide design and engineering as a means for linking molecular driving forces to self-assembled structure and macroscopic properties [Frederix et al, 2015;Tang et al, 2019a;V. Alegre-Requena et al, 2019;Prhashanna et al, 2019;Wang et al, 2020;Hilderbrand et al, 2021]. Using MD, the molecular interactions controlling peptide self-assembly can be probed such as hydrogen bonding and pi-pi stacking, thus informing new peptide designs and their impact on hierarchical structures spanning multiple length scales (e.g., peptide oligomerization and hydrogel assembly) [Li et al, 2014;Mansbach and Ferguson, 2017;Condon and Jayaraman, 2018;Taylor et al, 2020;Taylor et al, 2022].…”