Figure 1.

Rational Coarse Grain Models of PEG-PCL and Taxol with Free Energy Calculations. A. Based on all-atom computations, the diblock copolymer is modeled with one CG bead per ethylene glycol monomer and three CG beads per caprolactone monomer plus one interfacial CG bead between the two blocks. Taxol’s CG model maps 3–5 heavy atoms into each CG bead. Supplemental Tables 1 and 2 provide mapping details. B, C. Spherical micelle and Worm micelle cross-section used for thermodynamic integration with Taxol constrained near the interface. The block copolymer is PEG₂₀₀₀–PCL₅₀₀₀,and PEG in orange is shown with its hydration layer of CG water. Taxol’s aromatic groups orient toward the core. The orange arrow indicates the symmetry axis of the worm micelle. D, E. Thermodynamic integration constrains Taxol at a radial position r from the center of mass of a micelle and measures the constraint Force vs r. The core dimensions of Sphere and Worm micelles at 0.05% PCL density are indicated schematically with gray bars, and the transition to water is taken at 0.01% PEG density, which is also close to the plateau density for bulk water. The change in Taxol free energy ΔG(r) is determined relative to the center of the micelle, although the minimum free energy for the Worm is close to the PEG-PCL interface. F. The partition coefficient for Taxol transferred into water from each micelle is calculated, and the partition ratio (Worm/ Sphere) agrees with experiments.