Simulations of the Upper Critical Solution Temperature Behavior of Poly(ornithine-co-citrulline)s Using MARTINI-Based Coarse-Grained Force Fields

Poly­(ornithine-co-citrulline)­s are ureido-based polymers, which were shown to exhibit tunable upper critical solution temperature (UCST) behavior, a property that can be exploited to develop thermoresponsive nanoparticles for controlled drug delivery systems. To gain insight into the driving forces that govern the formation and dissolution processes of poly­(ornithine-co-citrulline) nanoparticles, a molecular dynamics (MD) simulation study has been carried out using MARTINI-based protein coarse-grained models. Multi-microsecond simulations at temperatures ranging from 280 to 370 K show that the fully reparametrized version 3.0 of MARTINI force field is able to capture the dependence on temperature of poly­(ornithine-co-citrulline) aggregation and dissolution, while version 2.2 could not account for it. Furthermore, the phase separation observed in these simulations allowed us to extrapolate a phase diagram based on the Flory–Huggins theory of polymer solution, which could help in future rational design of drug delivery nanoparticles based on poly­(amino acid)­s.