The partition coefficient (P) is an important parameter which represents the ratio of the solubility between polar and apolar phases, such as the water and n-octanol. (see Figure ) The logarithm of partition coefficient, i.e., log P, is usually taken as an indicator for screening out promising drug and material candidates in environmental science and pharmacology. Among some theoretical models, the log P parameter is also associated with other molecular properties, such as the aqueous solubility (log S), the distribution coefficient (log D), and Lipophilic Efficiency (LiPE). It was demonstrated that entropy may contribute to significant changes in the solubility of the nanocrystalligands complexes. In addition, in the polar phase, the solute polarizability and polarity are much more sensitive to the partition coefficient. The delicate balance between the entropy and the polarity in transporting small drug from phase of water to lipid was also revealed by our molecular dynamics (MD) simulations with both implicit and explicit polarization models . However, the time-consuming MD simulations of the solvation equilibrium in both polar and non-polar phases are impossible to realize the high-throughput screening of promising drugs and material candidates. Thus, an efficient model for log P prediction is highly desired to take the explicit polarization and entropy into considerations.