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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Barakat, M.T., Dean, P.M. The atom assignment problem in automated de novo drug design. 4. Tests for site-directed fragment placement based on molecular complementarity. J Computer-Aided Mol Des 9, 448–456 (1995). https://doi.org/10.1007/BF00124002
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DOI: https://doi.org/10.1007/BF00124002