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    NEWLEAD

    Vincenzo Tschinke
    Novartis Pharma AG

    N. Claude Cohen
    Synergix Ltd.

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    Abstract

    NEWLEAD [1] is a computer program for the automatic
    generation of candidate structures. The input for the program
    is a set of fragments in the three-dimensional orientation
    corresponding to a given pharmacophore model. The treatment
    consists in connecting the fragments with spacers assembled
    from small chemical entities (atoms, chains or ring moieties).
    The results are new structures containing the fragments in
    the orientation defined in the input. The program offers
    the opportunity of rapidly applying a pharmacophore model
    in drug-design by generating automatically a set of chemical
    sructures conforming to the model.

    We have tested [1] the program on several sets of input fragments,
    each comprising selected functional groups obtained from the
    bio-active conformations of reference molecules available from
    the literature. In addition to the expected solutions, the
    program can generate new structures that are chemically
    unrelated to the reference molecules. This provides an
    unbiased starting point for the design of new generations
    of lead structures. The treatment is very fast, because only
    a few bonds are created between building blocks already having
    ideal geometries.

    The user should define the input fragments based on a valid
    pharmacophore. A library of spacers to connect the fragments
    is provided with the software. The user can partly influence
    the outcome of a program run by defining preferred connection
    points, geometric parameters and types of atoms for the
    connections. The output results are clustered based on the
    similarity of the connecting spacers.

    The ability to generate rapidly a variety of molecules
    conforming to a three-dimensional pharmacophore model
    makes NEWLEAD a useful tool with wide applicability in
    rational drug design, including the areas of molecular
    mimicry and peptidomimetism.

[1] Tschinke, V.; Cohen N.C. The NEWLEAD Program: A New Method
    for the Design of Candidate Structures from Pharmacophoric
    Hypotheses. J. Med.Chem. 1993, 36, 3863-3870.

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    Instructions

 a) To extract the data, place the file 'newlead.tar.gz' in
    a convenient directory, then decompress it:

    gzip -dc newlead.tar.gz > newlead.tar

    tar xvf newlead.tar

 b) To install the program, follow the instructions in the
    file 'NEWLEAD_README'

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Modified: Mon Dec 11 22:19:02 2000 GMT
Page accessed 9063 times since Tue Dec 14 18:54:49 1999 GMT