Hydration thermodynamics of cytosolic phospholipase A2 IVA predict its membrane-associated parts and its highly hydrated binding site

During biological events, the water molecules associated with the protein are re-oriented to adapt to the new conditions, inducing changes in the system's free energy. The characterization of water structure and thermodynamics may facilitate the prediction of certain biological events, such as the binding of a ligand and the membrane-associated parts of a protein. In this computational study, we calculated the hydration thermodynamics of cytosolic phospholipase A2 group IV (GIVA cPLA2) to study the hydration properties of the protein's surface and binding pocket. Hydrophobicity scales and the Grid Inhomogeneous Solvation Theory (GIST) tool were employed for the calculations. The hydrophobic areas of the protein's surface were predicted more accurately with the GIST method rather than with the hydrophobicity scales. Based on this, a model of the protein-membrane complex was constructed. In addition, the calculation revealed the highly hydrated binding pocket that further contribute to our understanding of the ligands' binding.Communicated by Ramaswamy H. Sarma.