*3.2. Molecular Dynamics Simulations*

MD simulations of the 3HF/γ-CD complexes in Form I and Form II using the four different initial structures (eight complexes in total) were carried out using the AMBER16 program package [57]. The partial atomic charges and parameters of 3HF were generated in accordance with the previous standard procedures [58–60]. The general AMBER force field [61] and the Glycam06j carbohydrate force field [62] were applied for 3HF and γ-CD,

respectively. The models were solvated by a truncated octahedral box of TIP3P water molecules with a spacing distance of 15 Å from complex. Afterward, all added water molecules were minimized using 1000 steps of steepest descent (SD) and continued by 3000 steps of conjugated gradient (CG). Next, the minimizations with the same steps were performed on the whole system. All studied models were heated up from 10 K to 298 K with a constant volume ensemble (NVT) for 100 ps and followed by all-atom MD simulations with a constant pressure ensemble (NPT) at 1 atm and 298 K for 300 ns. All chemical bonds involving hydrogen were constrained using the SHAKE algorithm [63]. The particle mesh Ewald's method [64] was performed for the treatment of the long-range interactions. The cpptraj module of AMBER16 program was used to calculate the root-mean-square displacement (RMSD), the radius of gyration (Rgyr), and the distance between guest and host molecules as well as the radial distribution function (RDF).
