Cresset's inspirational FieldTemplater.application allows the modeller or
medicinal chemist to generate hypotheses for the bioactive conformation of
ligands from 2D structures alone. Given three or more active molecules,
FieldTemplater can suggest not only what the bioactive conformation of the
molecules is, but also the relative alignment of the different molecules
in the binding site.

FieldTemplater.builds hypotheses for the bioactive conformation in the
following way. First it reads a set of 2D active ligands and undertakes a
conformational exploration of each using XedeX. If you have a preferred
conformation explorer other than XedeX. then you can read in a
pre-prepared set of conformations instead. FieldTemplater.then analyses
the conformational sets to find inter-molecular pairs of conformations with
a high molecular field similarity (and hence similar shape/binding properties).
These pairs are then used to build and optimise a set of hypotheses for how all
(or most) of the molecules could bind to a common active site. The user is
presented with a small set of binding hypotheses for review.

For example, give FieldTemplater.the three HIV-1 RT inhibitors shown on the
left (from 2D drawings or sd files), and get back the alignment shown on the
right (RMS 1.2A to the x-ray alignment):

Download File Size:8.85 MB

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