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Ross G.A.,University of Oxford | Morris G.M.,Inhibox Inc. | Biggin P.C.,University of Oxford
PLoS ONE | Year: 2012

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.


Armstrong M.S.,Inhibox Inc. | Morris G.M.,Inhibox Inc. | Finn P.W.,Inhibox Inc. | Sharma R.,Inhibox Inc. | And 3 more authors.
Journal of Computer-Aided Molecular Design | Year: 2010

We present ElectroShape, a novel ligand-based virtual screening method, that combines shape and electrostatic information into a single, unified framework. Building on the ultra-fast shape recognition (USR) approach for fast non-superpositional shape-based virtual screening, it extends the method by representing partial charge information as a fourth dimension. It also incorporates the chiral shape recognition (CSR) method, which distinguishes enantiomers. It has been validated using release 2 of the Directory of useful decoys (DUD), and shows a near doubling in enrichment ratio at 1% over USR and CSR, and improvements as measured by Receiver Operating Characteristic curves. These improvements persisted even after taking into account the chemotype redundancy in the sets of active ligands in DUD. During the course of its development, ElectroShape revealed a difference in the charge allocation of the DUD ligand and decoy sets, leading to several new versions of DUD being generated as a result. ElectroShape provides a significant addition to the family of ultra-fast ligand-based virtual screening methods, and its higher-dimensional shape recognition approach has great potential for extension and generalisation. © 2010 Springer Science+Business Media B.V.


Armstrong M.S.,Inhibox Inc. | Finn P.W.,Inhibox Inc. | Morris G.M.,Inhibox Inc. | Richards W.G.,University of Oxford
Journal of Computer-Aided Molecular Design | Year: 2011

In a previous paper, we presented the Electro- Shape method, which we used to achieve successful ligandbased virtual screening. It extended classical shape-based methods by applying them to the four-dimensional shape of the molecule where partial charge was used as the fourth dimension to capture electrostatic information. This paper extends the approach by using atomic lipophilicity (alogP) as an additional molecular property and validates it using the improved release 2 of the Directory of Useful Decoys (DUD). When alogP replaced partial charge, the enrichment results were slightly below those of ElectroShape, though still far better than purely shape-based methods. However, when alogP was added as a complement to partial charge, the resulting five-dimensional enrichments shows a clear improvement in performance. This demonstrates the utility of extending the ElectroShape virtual screening method by adding other atom-based descriptors. © 2011 Springer Science+Business Media B.V.


Inhibox Inc. | Entity website

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 ...


Inhibox Inc. | Entity website

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 ...


Inhibox Inc. | Entity website

The technology that has made Scopiusthe worlds top screening database can be implemented on user sites for the proprietary data. This includes: Compound Collection InhibOx can create from your compounds a private database with 3D models, full conformational analysis, calculation of all shape, charge and descriptor keys and your key compound data, to allow fast and flexible search across all of your available compounds Virtual Library Build we can take your reagent sets and your approved chemistries and combine them to build a virtual library of all your accessible compounds ...


Inhibox Inc. | Entity website

Oxford, UK 23rd July, 2013 InhibOx, the computer-aided drug design company, has been awarded funding of 1 million by the European Commissions 7th Framework Programme as part of a 4.1 million consortium project for the preclinical development of novel treatments for multi-drug resistant bacterial infections ...


Inhibox Inc. | Entity website

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 ...


PubMed | Inhibox Inc.
Type: Journal Article | Journal: Journal of computer-aided molecular design | Year: 2010

We present ElectroShape, a novel ligand-based virtual screening method, that combines shape and electrostatic information into a single, unified framework. Building on the ultra-fast shape recognition (USR) approach for fast non-superpositional shape-based virtual screening, it extends the method by representing partial charge information as a fourth dimension. It also incorporates the chiral shape recognition (CSR) method, which distinguishes enantiomers. It has been validated using release 2 of the Directory of useful decoys (DUD), and shows a near doubling in enrichment ratio at 1% over USR and CSR, and improvements as measured by Receiver Operating Characteristic curves. These improvements persisted even after taking into account the chemotype redundancy in the sets of active ligands in DUD. During the course of its development, ElectroShape revealed a difference in the charge allocation of the DUD ligand and decoy sets, leading to several new versions of DUD being generated as a result. ElectroShape provides a significant addition to the family of ultra-fast ligand-based virtual screening methods, and its higher-dimensional shape recognition approach has great potential for extension and generalisation.

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