Simulations of Self-Assembly in Globular Protein-Polymer Conjugates

Globular protein-polymer conjugates, a type of block copolymer where one block is a fully-folded globular protein and the other is a synthetic polymer, have been demonstrated to self-assemble into a wide variety of biofunctional nanostructures analogous to those formed by traditional block copolymers. However, the phase behavior of bioconjugates differs dramatically from their better-studied counterparts. Herein, we develop a simple molecular model of the bioconjugates based on a hard sphere colloid (the protein) conjugated to a soft sphere colloid (the polymer). We examine the self-assembly of these dumbbell molecules and investigate the phase behavior of the protein-polymer conjugates using three-dimensional molecular dynamics simulations. This model shows lyotropic self-assembly with increasing concentration, and several different phases can be observed that are analogous to those seen in experiments. Modifying the size of the soft sphere mimics changes in polymer molar mass, while changes in the interaction potentials between different blocks enable exploration of the relative role of polymer-polymer, protein-protein, and protein-polymer interactions in driving self-assembly.