Molecular dynamics studies of PEGylated α-helical coiled coils and their self-assembled micelles.

We performed coarse-grained (CG) molecular dynamics simulations of trimeric α-helical coiled coils grafted with poly(ethylene glycol) (PEG) of different sizes and conjugate positions and the self-assembled micelle of amphiphilic trimers. The CG model for the trimeric coiled coil is verified by comparing the α-helical structure and interhelical distance with those calculated from all-atom simulations. In CG simulations of PEGylated trimers, the end-to-end distances and radii of gyration of PEGs grafted to the sides of peptides become shorter than those of free PEGs in water, which agrees with experiments. This shorter size of the grafted PEGs is also confirmed by calculating the thickness of the PEG layer, which is less than the size of the mushroom. These indicate the adsorption of PEG chains onto coiled coils since hydrophobic residues in the exterior sites of coiled coils tend to be less exposed to water and thus interact with PEGs, leading to the compact conformation of adsorbed PEGs. Simulations of the self-assembly of amphiphilic trimers show that the randomly distributed trimers self-assemble to micelles. The outer radius and hydrodynamic radius of the micelle, which were calculated respectively from radial densities and diffusion coefficients, are ∼7 nm, in agreement with the experimental value of ∼7.5 nm, while the aggregation number of amphiphilic molecules per micelle is lower than the experimentally proposed value. These simulations predict the experimentally measured size of PEGs grafted to the trimeric coiled coils and their self-assembled amphiphilic micelles and suggest that the aggregation number of the micelle may be lower, which needs to be confirmed by experiments.