ProBiS H2O MD Approach for Identification of Conserved Water Sites in Protein Structures for Drug Design‡

[Image: see text] The ProBiS H2O MD approach for identification of conserved waters and water sites of interest in macromolecular systems, which is becoming a typical step in a structure-based drug design or macromolecular study in general, is described. This work explores an extension of the ProBiS H2O approach introduced by Jukič et al. Indeed, water molecules are key players in the interaction mechanisms of macromolecules and small molecules and play structural roles. Our earlier developed approach, ProBiS H2O, is a simple and transparent workflow for conserved water detection. Here we have considered generalizing the idea by supplementing the experimental data with data derived from molecular dynamics to facilitate work on less known systems. Newly developed ProBiS H2O MD workflow uses trajectory data, extracts and identifies interesting water sites, and visualizes the results. ProBiS H2O MD can thus robustly process molecular dynamic trajectory snapshots, perform local superpositions, collect water location data, and perform density-based clustering to identify discrete sites with high conservation of water molecules. This is a new approach that uses experimental data in silico to identify interesting water sites. Methodology is fast and water-model or molecular dynamics software independent. Trends in the conservation of water molecules can be followed over a variety of trajectories, and our approach has been successfully validated using reported protein systems with experimentally observed conserved water molecules. ProBiS H2O MD is freely available as PyMOL plugin at http://insilab.org.