The atom assignment problem in automated de novo drug design. 4. Tests for site-directed fragment placement based on molecular complementarity |
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Authors: | M T Barakat P M Dean |
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Institution: | (1) Drug Design Group, Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ Cambridge, U.K. |
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Abstract: | Summary Three previous papers in this series have outlined an optimization method for atom assignment in drug design using fragment placement. In this paper the procedure is rigorously tested on a selection of five ligand-protein co-crystals. The algorithm is presented with the molecular graph of the ligand, and the electrostatic/hydrophobic potential of the site, with the aim of creating a placement on the molecular graph which is as electrostatically complementary or hydrophobically similar to the site as possible. Various designer options were tested, including, where appropriate, hydrogen bonding and a restricted number of halogens. In most cases, the placement obtained was at least as good as the native ligand, if not significantly better. |
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Keywords: | De novo drug design Molecular electrostatic potential Molecular complementarity Molecular similarity |
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