Characterizing the Interactions Between Synthetic Random Heteropolymers with Molecular Dynamics

Synthetic random heteropolymers (RHPs) are amphiphilic, globular macromolecules that provide insight into protein behavior. While RHPs are inspired by proteins, the RHPs considered here are simpler systems composed of methacrylate-based building blocks without deterministic sequence-to-structure correlations. We use atomistic molecular dynamics simulations to show how sequence composition and surface chemistry impact the energetics and dynamics of inter-RHP interactions in water, including interaction time, solvent accessibility, and interface compositions. Our results show that although hydrophobic surface content is an important factor in the initiation of RHP dimerization, intermolecular contacts are not limited to hydrophobic regions. We also found that the dynamics of RHP remodeling in multi-chain assemblies are similar to those in single-chains on simulation timescales. Finally, we contextualize our results using methodologies for more widely-studied protein-protein interactions.