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PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules

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Summary

An approach to de novo molecular design, PRO_LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies-placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO_LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.

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Authors and Affiliations

  1. Proteus Molecular Design Ltd., Proteus House, Lyme Green Business Park, SK11 oJL, Macclesfield, Cheshire, U.K.

    David E. Clark, David Frenkel, Stephen A. Levy, Jin Li, Christopher W. Murray, Barry Robson, Bohdan Waszkowycz & David R. Westhead

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  1. David E. Clark
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  2. David Frenkel
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  4. Jin Li
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  6. Barry Robson
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  7. Bohdan Waszkowycz
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  8. David R. Westhead
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Clark, D.E., Frenkel, D., Levy, S.A. et al. PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules. J Computer-Aided Mol Des 9, 13–32 (1995). https://doi.org/10.1007/BF00117275

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  • DOI: https://doi.org/10.1007/BF00117275

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