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Oxford, United Kingdom

Ross G.A.,University of Oxford | Morris G.M.,Inhibox Inc. | Biggin P.C.,University of Oxford

Water plays a critical role in ligand-protein interactions. However, it is still challenging to predict accurately not only where water molecules prefer to bind, but also which of those water molecules might be displaceable. The latter is often seen as a route to optimizing affinity of potential drug candidates. Using a protocol we call WaterDock, we show that the freely available AutoDock Vina tool can be used to predict accurately the binding sites of water molecules. WaterDock was validated using data from X-ray crystallography, neutron diffraction and molecular dynamics simulations and correctly predicted 97% of the water molecules in the test set. In addition, we combined data-mining, heuristic and machine learning techniques to develop probabilistic water molecule classifiers. When applied to WaterDock predictions in the Astex Diverse Set of protein ligand complexes, we could identify whether a water molecule was conserved or displaced to an accuracy of 75%. A second model predicted whether water molecules were displaced by polar groups or by non-polar groups to an accuracy of 80%. These results should prove useful for anyone wishing to undertake rational design of new compounds where the displacement of water molecules is being considered as a route to improved affinity. © 2012 Ross et al. Source

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Cloud-Enabled Drug Discovery Drug discovery in the 21st century is undergoing the most dramatic change it has ever seen. Pharma companies are globalizing their R&D capabilities, seeking new collaboration partners and outsourcing activities from simple tasks to complete projects ...

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Introduction Ligand-protein docking methods attempt to identify optimal positions, orientations and conformations of a ligand or small molecule with respect to a given protein receptor or enzyme. InhibOx offers extensive expertise and a range of solutions in ligand-protein docking ...

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LOx offers a new pharmacophoric linking approach, integrated with Scopius, the largest available curated 3D compound and fragment database Oxford, UK, October 28th, 2010. InhibOx Ltd today announces LOx 2 ...

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Computer-Aided Drug Design (CADD) is the key focus of InhibOx: our people have decades of experience in developing new methods and applying them. We have worked on a variety of fixed-term and on-going projects for our clients, across a range of therapeutic areas, bringing a wealth of CADD experience and know-how with us ...

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