Investigation of Self‐Assembly of Symmetric and Asymmetric Peptide Bolaamphiphiles by COSMO‐RS and Atomistic Simulations and Their Interactions with POPC Bilayers

Abstract

AbstractIn this work, eight new peptide bolaamphiphiles (PbAs) are designed containing polar (serine or threonine) and nonpolar amino acid head groups (tryptophan or tyrosine) connected by varying aliphatic carbon chains of different lengths and saturation. The physicochemical properties of the bolaamphiphiles are examined by COSMO‐RS to determine sigma profiles, potential, and sigma surfaces. Self‐assembly is studied using atomistic molecular dynamic simulations under protonated and deprotonated conditions. To mimic physiological conditions, simulations are also carried out in the presence of sodium chloride and the impact of salt on the self‐assembly process is also studied. In general, hydrophobic PbAs are found to form higher‐order supramolecular structures while PbAs connected by shorter chains or hydrophilic head groups form globular, more compact structures. Self‐assembly is more favorable when the PbAs are protonated. Membrane interactions are then studied using MD simulations and the results indicate that the hydrophobic PbAs interact more favorably with the POPC membrane surfaces. These simulations provide insights about the intricate interactions and properties of the PbAs and shed light on the ability to form fine‐tuned structures at the nanoscale. This study may lead to the development of novel PbAs for potential applications in a wide variety of biological applications.