Abstract
New approaches are needed that can help decrease the unsustainable failure in small-molecule drug discovery. Ligand Efficiency Indices (LEI) are making a great impact on early-stage compound selection and prioritization. Given a target-ligand database with chemical structures and associated biological affinities/activities for a target, the AtlasCBS server generates two-dimensional, dynamical representations of its contents in terms of LEI. These variables allow an effective decoupling of the chemical (angular) and biological (radial) components. BindingDB, PDBBind and ChEMBL databases are currently implemented. Proprietary datasets can also be uploaded and compared. The utility of this atlas-like representation in the future of drug design is highlighted with some examples. The web server can be accessed at http://ub.cbm.uam.es/atlascbs and https://www.ebi.ac.uk/chembl/atlascbs.
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Acknowledgments
The assistance of the ChEMBL group in facilitating the data extraction for the AtlasCBS database is greatly appreciated. This work was supported by grants from Comunidad Autónoma de Madrid (S-BIO-0214-2006 and S2010-BMD-2457 to F.G. and A.M.), Fundación Severo Ochoa (AMAROUTO program to A.M.) and the Spanish Ministerio de Educación (FPU AP2009-0203 to A. C. and SAB2010-0037 to C. A-Z). The suggestions and comments from the reviewers of this work are greatly appreciated. The insightful comments, discussions and suggestions of Daniel Blasi of the Platform of Drug Discovery (Dr. J. Quintana, Director) within the Parc Científic Barcelona are also appreciated. We gratefully acknowledge the help of Mark Davies, John Overington and Peter Rose in our efforts to relate AtlasCBS to ChEMBL and PDB.
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Cortés-Cabrera, Á., Morreale, A., Gago, F. et al. AtlasCBS: a web server to map and explore chemico-biological space. J Comput Aided Mol Des 26, 995–1003 (2012). https://doi.org/10.1007/s10822-012-9587-5
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DOI: https://doi.org/10.1007/s10822-012-9587-5