Thermodynamic Integration Hydration Free Energy Calculations. Simulations were carried out with one-step thermodynamic integration with softcore potentials and linear scaling using the pmemd.cuda MD engine from Amber18 . Ligands were decoupled from the solvation box in 21 evenly spaced λ) of a -windows ranging from 0.0 to 1.0 in intervals of 0.05.