The incorporation of explicit solvent in molecular docking is a critical aspect that significantly influences the accuracy of docking predictions. This approach involves explicitly including water molecules or other solvent molecules in the docking simulations to more accurately model the real-life conditions under which molecular interactions occur. The presence of solvent can affect the conformation of the ligand and the receptor, as well as the interaction between them, making the consideration of solvent effects essential for realistic docking studies. Water molecules often play a crucial role in ligand recognition and complex stabilization for both nucleic acids and proteins. The polarization effects caused by the solvent can significantly impact the docking process, especially for nucleic acids where the phosphate groups and counter ions like Mg + 2 or K + influence the water molecules and functional groups of drugs. Despite the recognized importance of explicit solvent in docking, incorporating water molecules into the docking process presents significant challenges. The large, solvent-accessible interface of macromolecules makes it extremely challenging to accurately model the effects of water molecules within a reasonable computational timeframe . It is worth noting that even the water model used can affect the calculated parameters in the simulations .