Effect of Polymer Conjugation Site on Stability and Self-Assembly of Coiled Coils

Conjugation of proteins with polymers has emerged as a new design technique to produce hybrid block copolymers with tailored hierarchical structures and desirable functionalities as well as greater stability. However, due to the sequence and chemistry dependence of the conjugation effects, it remains challenging to understand the overall effect of the location of polymer conjugation on supramolecular organization. As a step toward addressing this issue, here, we report coarse-grained molecular dynamics simulations of the supramolecular organization of coiled coil assemblies with terminal and side-chain conjugated alpha-helices. Our simulations indicate that helicity and thermal stability are preserved for both side and end polymer conjugation, but the steric hindrance by polymer chains influences the aggregation patterns of coiled coils in different ways, depending on the conjugation location. The aggregation number of assembled clusters decreases upon polymer conjugation, and this effect is more pronounced for side conjugation compared to end conjugation. Our results explain recent experimental findings on peptide-polymer conjugates and lay the groundwork for the design of protein assemblies with enhanced thermomechanical stability and controlled aggregation behavior in different environmental conditions.