WATCLUST: a new tool to improve the design of hydrophilic drugs based on protein-water interactions

ELÍAS LÓPEZ; DIEGO GAUTO; ARIEL PETRUK; VICTORIA DUMAS; JUAN PABLO ARCON; MARCELO MARTÍ; ADRIÁN TURJANSKI

Bariloche

Congreso; V Congreso Argentino de Bioinformática y Biología Computacional; 2014

Asociación Argentina de Bioinformática y Biología Computacional

Water molecules play an essential role in the structure and function of proteins. Water Sites (WS) are defined as confined space regions adjacent to the protein surface where the probability of finding a water molecule is higher than in the bulk solvent. The strategy used to determine the WS is adapted from our previous works [1,2]. Once determined and characterized the WS can constitute a good thermodynamic descriptor of ligand free energy binding. To elucidate the thermodynamic profile and itspotential contribution to ligand binding, a hydration site analysis program called WATCLUST has been developed. WATCLUST identifies hydration sites from a molecular dynamics simulation trajectory with explicit water molecules. The free energy profile of each hydration site is estimated by computing the enthalpy and entropy of the water molecule occupying a hydration site throughout the simulation. The results of the hydration site analysis can be displayed in VMD. WATCLUST thus presents an easy,and user friendly, analysis visualization tool to determine the WS and their properties that can be used by people in the structural bioinformatics field.