The van der Waals interactions are perturbed linearly across the full range of λ values such that λ = 0/1 corresponds to the van der Waals interactions fully turned off/on respectively. On the other hand, the electrostatic interactions remain extinguished between λ 0 and 0.45 and are perturbed linearly from λ 0.45 to 1. Further, we use twelve λ-windows for the removal of restraints on the ligand in the protein environment (when performed separately from ligand coupling) with λ = {1.0, 0.75, 0.5, 0.3, 0.2, 0.15, 0.1, 0.075, 0.05, 0.025, 0.01, 0.0}. Both these series of λ-windows are more closely spaced near λ = 0 due to the steeper energy gradient in the corresponding region of the phase space. When ligand coupling and removal of restraints in the protein environment are performed simultaneously, we use fifteen λ-windows = {0.0, 0.01, 0.05, 0.1, 0.2,....,0.9, 0.95, 0.99, 1.0} (with the strength of restraints varying as 1 -λ).