Effect of Solvent Water Molecules on Human Serum Albumin Complex-Docked Paclitaxel by MM-PBSA Method.

Molecular modeling on solvation effect and interaction mechanism of the water molecules in the active site of protein affect significantly the interaction between protein and ligand. Detailed influence of water molecules in the active site of human serum albumin (HSA) on its paclitaxel complex as well as their interaction is essential for clinical studies. Molecular docking of both crystal-HSA and solvated-HSA with paclitaxel was performed in the present work. The docking result shows that paclitaxel is inserted more deeply in the binding pocket of crystal-HSA than in the same site of solvated-HSA, and more intermolecular H-bonds are formed in the shrunken binding site of solvated-HSA. The favorable docking energies also reflect that solvated-HSA model is more tightly integrated with paclitaxel than crystal-HSA. According to the MD results of solvated-HSA-paclitaxel, six intermolecular H-bonds have formed at the binding site, two of them linking with the water molecules. It proves that water molecules in the binding site have affected the interaction between protein and ligand significantly. The MD results for the two complexes also suggest that the solvated protein model will lead to a rather different binding complex.