Hard sphere-driven phase transitions in coarse-grained simulations of globular protein–polymer block copolymers

Although globular protein-polymer bioconjugates in solution have been shown to self-assemble into many of the same nanostructures observed for traditional coil-coil block copolymers, there are also key differences that appear to be universal across bioconjugate systems with different protein and polymer blocks. This suggests that factors originating from the coarse-grained shape of the molecules may play a key role in many of these behaviors. Here, coarse-grained molecular dynamics simulations of dumbbells consisting of a hard sphere, representing the protein, and a soft sphere, representing the polymer, were used to investigate the physics underlying self-assembly. This highly coarse-grained model captured many of the most notable features of the protein-polymer bioconjugate phase diagram, including compositional asymmetry and a lyotropic reentrant order-disorder transition. The hard sphere block was found to be an important determinant for phase diagram asymmetry, with the rigidity of the hard sphere prohibiting the formation of spheres and inverse phases. Furthermore, entropically driven hard sphere ordering at high concentrations appears to be correlated with a restriction in the rearrangement of the dumbbells into a well-ordered nanostructure, leading to the reentrant order-disorder transition into a weakly ordered phase. The insights from this model can inform the design of biomaterials that incorporate globular protein-polymer block bioconjugates.