Document 0085
 DOCN  M9480085
 TI    Three-dimensional pharmacophores from binding data.
 DT    9410
 AU    Doweyko AM; CIBA-GEIGY Corporation, Environmental Health Center,
       Farmington,; Connecticut 06032.
 SO    J Med Chem. 1994 Jun 10;37(12):1769-78. Unique Identifier : AIDSLINE
       MED/94293295
 AB    The application of HASL (hypothetical active site lattice) methodology
       has been successfully extended to generate putative pharmacophoric
       patterns in three dimensions capable of quantitatively predicting
       binding activity. The transformation of a HASL model to a pharmacophore
       is illustrated using pKi values published for 84 HIV-1 protease
       inhibitors. Starting with a HASL model generated at 2.00 A and
       containing 899 lattice points, a selective trimming process was used to
       identify significant lattice points. In this manner, a set of 11 points
       was found which represents a potential pharmacophoric pattern and
       predicts the pKi activity of the 84-inhibitor set with a correlation
       (r2) of 0.827. Furthermore, the locations of these points were found to
       coincide with a number of strategic binding areas within the known
       active site structure HIV-1 protease, thus providing a physical
       confirmation of their relevancy.
 DE    Binding Sites  HIV Protease Inhibitors/CHEMISTRY/METABOLISM
       HIV-1/ENZYMOLOGY  *Models, Chemical  *Structure-Activity Relationship
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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