All free energy calculations in this study have been performed using the TIES protocol that has been described in detail in our prior publications. Briefly, it involves performing an ensemble simulation at each intermediate alchemical state followed by ensemble averaging of the bootstrapped potential energy derivatives so obtained. Such averaged energy derivatives are then integrated using the principles of stochastic calculus to get the final free energy difference along with associated uncertainties using equation 2. The standard protocol is to perform an ensemble of 5 MD simulations at each λ window of length 4 ns and uses 13 λ-windows as follows: 0, 0.05, 0.1,....0.9, 0.95, 1. It should be noted that these standard settings for the TIES protocol were derived through a systematic study of the dependence of accuracy and precision of the TIES predictions on all these parameters. However, it should be noted that these standard values may need to be adjusted in some cases to control errors/uncertainties.