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Three-dimensional hydrogen-bond geometry and probability information from a crystal survey

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Summary

An extensive crystal survey of the Cambridge Structural Database has been carried out to provide hydrogen-bond data for use in drug-design strategies. Previous crystal surveys have generated 1D frequency distributions of hydrogen-bond distances and angles, which are not sufficient to model the hydrogen bond as a ligand-receptor interaction. For each hydrogen-bonding group of interest to the drug designer, geometric hydrogen-bond criteria have been derived. The 3D distribution of complementary atoms about each hydrogen-bonding group has been ascertained by dividing the space about each group into bins of equal volume and counting the number of observed hydrogen-bonding contacts in each bin. Finally, the propensity of each group to form a hydrogen bond has been calculated. Together, these data can be used to predict the potential site points with which a ligand could interact and there-fore could be used in molecular-similarity studies, pharmacophore query searching of databases, or de novo design algorithms.

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Authors and Affiliations

  1. Drug Design Group, Department of Pharmacology, University of Cambridge, Tonnis Court Road, CB2 1QJ, Cambridge, U.K.

    J. E. J. Mills & P. M. Dean

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  1. J. E. J. Mills
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  2. P. M. Dean
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Mills, J.E.J., Dean, P.M. Three-dimensional hydrogen-bond geometry and probability information from a crystal survey. J Computer-Aided Mol Des 10, 607–622 (1996). https://doi.org/10.1007/BF00134183

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  • DOI: https://doi.org/10.1007/BF00134183

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