W2W: Welcome to watclust!

Introduction

The WATCLUST plugin[1] combines the potential of Molecular Dynamics (MD) simulations data with statistical mechanics analysis in order to compute structural and thermodynamic properties of water molecules of solvation. Moreover, it allows to analyze them in a comparative view into the open source VMD interface.

The application goal is to perform the physicochemical analysis of water surrounding a protein (or other types of macromolecules). Starting with an MD simulation of a protein in explicit solvent, the software is able to find confined regions of space, adjacent to the protein, where there is a high probability of finding water molecules and to calculate thermodynamic properties relevant for different biophysical analysis, using inhomogeneous fluid solvation theory (IFST) [2-6]. Those sites where the probability of finding a water molecule is higher than in bulk are called water sites (WS).

An outstanding feature of the program is that it allows to transfer the WS information to the Autodock docking program in order to perform a biased docking[7] that improves ligand poses predictions for hydrophilic ligands.

 

References

1. López E.D., Arcon J.P., Gauto D.F., Petruk A.A., Modenutti C.P., Dumas V.G., Marti M.A., Turjanski A.G. WATCLUST: a tool for improving the design of drugs based on protein-water interactions. Bioinformatics 2015, 31(22), 3697–3699. DOI: 10.1093/bioinformatics/btv411

2. Lazaridis, T. Inhomogeneous Fluid Approach to Solvation Thermodynamics. 1. Theory. J. Phys. Chem. B. 1998, 102(18), 3531–3541. DOI: 10.1021/jp9723574

3. Li, Z.; Lazaridis, T. The Effect of Water Displacement on Binding Thermodynamics: Concanavalin A. J. Phys. Chem. B. 2005, 109(1), 662–670. DOI: 10.1021/jp0477912

4. Huggins, D.J.; Payne, M.C. Assessing the Accuracy of Inhomogeneous Fluid Solvation Theory in Predicting Hydration Free Energies of Simple Solutes. J. Phys. Chem. B. 2013, 117(27), 8232–8244. DOI: 10.1021/jp4042233

5. Huggins, D.J. Application of Inhomogeneous Fluid Solvation Theory to Model the Distribution and Thermodynamics of Water Molecules around Biomolecules. Phys. Chem. Chem. Phys. 2012, 14, 15106-15117. DOI: 10.1039/C2CP42631

6. Nguyen, C.N.; Young, T.K.; Gilson, M.K. Grid Inhomogeneous Solvation Theory: Hydration Structure and Thermodynamics of the Miniature Receptor cucurbit[7]uril. J. Chem. Phys. 2012. 137(4): 044101. DOI: 10.1063/1.4733951

7. Arcon, J.P.; Modenutti, C.P.; Avendaño, D.; Lopez, E.D.; Defelipe, L.A.; Ambrosio, F.A.; Turjanski, A.G.; Forli, S.; Marti, M.A. AutoDock Bias: improving binding mode prediction and virtual screening using known protein–ligand interactions. Bioinformatics 2019. 35(19), 3836-3838. DOI: 10.1093/bioinformatics/btz152