18.45 W-UC (6:3) 27.34 W-UC (8:4) 10.37 A comparison between the probability distributions is also provided in the supplementary information (Fig ) using both the protocols for all the different systems. Table represents the percentage of increment in 〈(𝑞 𝑡𝑒𝑡 ) 𝑠𝑦𝑠𝑡𝑒𝑚 〉 while going from Protocol-1 to Protocol-2. An increasing rise in the enhancement is observed going from W-UC (2:1) to W-UC (6:3), but the enhancement drops drastically to ~10% from ~27% from W-UC (6:3) to W-UC (8:4). It can be attributed to the fact that, while accounting for the system W-UC (8:4), the number of water molecules in the system is negligibly small and the environment is highly crowded. Even in the case of Protocol-2, water molecules cannot suitably coordinate with electronegative hetero. This gets reflected in a considerably lesser enhancement of the average TOP value from W-UC (6:3) to W-UC (8:4).