Optimizing Protein–Polymer Interactions in a Poly(ethylene glycol) Coarse-Grained Model

Increasing demand for hybrid materials that merge the synthetic and biological areas in drug industries requires in-depth knowledge of the individual components and their contributions to these complexes. Coarse-grained (CG) models developed for proteins and polymers exist, yet there is a lack of understanding of the cross interactions when these two groups of materials integrate to build a complex. In this work, we characterized the nonbonded interactions between poly(ethylene glycol) (PEG) and amino acids in a Martini CG model utilizing state-of-the-art quantum mechanics calculations of interaction energies. The parameter set proposed, was validated by assessing the polymer density in the vicinity of individual amino acids obtained from available all-atomistic molecular dynamic simulations of plasma proteins. Our results revealed the necessity of protein–polymer interaction parameterization at the CG level to avoid overestimation of polymer association when employing other PEG models within the Martini ...