Calculation of Thermodynamic Properties of Bound Water Molecules.

Water molecules in the binding site of a protein significantly influence protein structure and function, for example, by mediating protein-ligand interactions or in form of desolvation as driving force for ligand binding. The knowledge about location and thermodynamic properties of water molecules in the binding site is crucial to the understanding of protein function. This chapter describes the method of calculating the location and thermodynamic properties of bound water molecules from molecular dynamics (MD) simulation trajectories. Thermodynamic profiles of water molecules can be calculated either with or without the presence of a bound ligand based on the scientific problem. The location and thermodynamic profile of hydration sites mediating the protein-ligand interactions is important for understanding protein-ligand binding. The protein desolvation free energy can be estimated for any ligand by summation of the hydration site free energies of the displaced hydration sites. The WATsite program with an easy-to-use graphical user interface (GUI) based on PyMOL was developed for those calculations and is discussed in this chapter. The WATsite program and its PyMOL plugin are available free of charge from http://people.pharmacy.purdue.edu/~mlill/software/watsite/version3.shtml .

WATsite2.0 with PyMOL Plugin: Hydration Site Prediction and Visualization.

Water molecules in the binding site of a protein significantly influence protein structure and function, for example, by mediating protein-ligand interactions or due to water displacement as driving force for ligand binding. The knowledge about location and thermodynamic contributions of binding site water molecules is crucial for understanding protein function. WATsite is a hydration site analysis program that was developed together with an easy-to-use graphical user interface (GUI) based on PyMOL. WATsite identifies hydration sites from a molecular dynamics (MD) simulation trajectory with four different types of explicit water molecules. Hydration sites can be identified with or without the presence of a bound ligand dependent on the scientific problem. The protein desolvation free energy can be estimated for any ligand by summation of the hydration site free energies of the displaced hydration sites. The location and thermodynamic profile of hydration sites mediating the protein-ligand interactions is important for understanding protein-ligand binding. The WATsite program and GUI are available free of charge from http://people.pharmacy.purdue.edu/~mlill/software/watsite/version2.shtml .