We report the development of a coarse grained molecular model within the MARTINI framework for Polycaprolactone (PCL), a biodegradable hydrophobic polymer. PCL is applied in drug delivery, especially in the form of self-assembled nanoparticles. Hydrophobic drugs that cannot be directly administered into the systemic circulation, can be encapsulated in the hydrophobic PCL core of these self-assembled nanoparticles, thereby enabling their delivery. Computational studies on the self-assembly of molecules involving PCL, necessitate the development of a robust coarse grained model.
We parametrized the intramolecular interactions in the coarse grained model by mapping onto the OPLS-united-atom (OPLS-UA) rendition of PCL. The coarse grained model for PCL was validated by examining the polymer chain conformation, as well as by molecular dynamics simulations of self-assembled micelles formed by an amphiphilic Methoxy polyethylene glycol-(block)-Polycaprolactone (MePEG-b-PCL) linear diblock copolymer. We compared the polymer chain conformation of the coarse-grained polymer model in water with that of an OPLS-all atom (OPLS-AA) rendition, for different polymer chain lengths. We found that the average end to end distance, radius of gyration and other key properties showed excellent agreement between the coarse grained and all atom models. We also studied the self-assembly of the amphiphilic (MePEG17-b-PCL3) diblock copolymer system, using an existing MARTINI coarse grained model for MePEG , and the model developed in this work, for PCL. We observed a gradual self-assembly of the block copolymer into large spherical micelles that consisted of a hydrophobic PCL core surrounded by MePEG. We computed the aggregation number of the micelles and their hydrodynamic radii. We also determined the critical micelle concentration (CMC) of MePEG17-b-PCL2 diblock copolymers, which was found in a reasonable agreement with experiment.
Fig.1. Self-assembly of MePEG17-b-PCL3 linear diblock copolymers. Snapshots at the initial and final simulation time. (Color codes: MePEG-Green, PCL-Red)
 Hwankyu Lee, Alex H. de Vries, Siewert-Jan Marrink and Richard W. Pastor, J. Phys. Chem. B, 2009, 113 (40), pp 13186-13194.