Influence of salt and temperature on the self-assembly of cyclic peptides in water: a molecular dynamics study

It is found in the literature that cyclic peptides (CPs) are able to self-assemble in water to form cyclic peptide nanotubes (CPNTs) and are used extensively in the field of nanotechnology. Several factors influence the formation and stability of these nanotubes in water. However, an extensive study of the contribution of several important factors is still lacking. The purpose of this study is to explore the effect of temperature and salt (NaCl) on the association tendency of CPs. Furthermore, the self-association behavior of CPs in aqueous solutions at various temperatures is also thoroughly discussed. Cyclo-[(Asp-D-Leu-Lys-D-Leu)₂] is considered for this study and a series of classical molecular dynamics (MD) simulations at three different temperatures, viz. 280 K, 300 K, and 320 K, both in pure water and in NaCl solutions of different concentrations are carried out. The calculations of radial distribution functions, preferential interaction parameters, cluster formation and hydrogen bonding properties suggest a strong influence of NaCl concentration on the association propensity of CPs. Low NaCl concentration hinders CP association while high NaCl concentration facilitates the association of CPs. Besides this, the association of CPs is found to be enhanced at low temperature. Furthermore, the thermodynamics of CP association is predominantly found to be enthalpy driven in both the presence and absence of salt. No crossover between enthalpy and entropy in CP association is observed. In addition, the MM-GBSA method is used to investigate the binding free energies of the CP rings that self-assembled to form nanotube like structures at all three temperatures.