Self-Assembly of Protein-based Block Copolymers – A Minimal Coarse-grained Model

Protein-based block copolymers self-assemble into various nanostructures that are instrumental in developing next-generation biocatalysts and biosensors. Phase behavior of such block copolymers depends upon several parameters: temperature, blocks volume fractions, conjugate concentration in solution, protein shape and charge density, and multiple binary interaction parameters. In this work, a highly coarse-grained dumbbell model is developed in which protein is represented as a hard sphere linked to a soft sphere denoting a flexible polymer coil. Molecular dynamics simulations are performed with both implicit and explicit solvent. It is observed that such a simple model, incorporating primarily the various binary interactions, forms all the different morphologies that are observed experimentally. Interestingly, the model also predicts a lyotropic re-entrant order-disorder transition that is peculiar to protein-based block copolymers compared to coil-coil block copolymers. Integral-equation state theories are used to compute the solvent-mediated interactions to understand the origin of re-entrant transition. This work sheds light on the key factors governing the phase behavior of protein-based block copolymer solutions.