The application of computational techniques in molecular design
The application of computational techniques in molecular design
An integrated series of techniques is described that allows the automatic construction of a diverse set of chemically reasonable and synthetically accessible molecules that are complementary to a given receptor model.
A general approach to characterising receptor targets in terms of excluded volumes and interaction sites is described that allows a variety of different systems, such as pharmacophores, enzyme active sites, signal receptors etc., to be modelled.
It is shown how novel molecules can be produced by initially constructing molecular skeletons that connect the functional groups, or larger molecular fragments, that characterise the interaction sites within the receptor model. Molecular skeletons can be built from a generic atom type, with a carbon geometry, in a two stage process. First an algorithm for linking separate molecular fragments with low energy acyclic chains that avoid the excluded volumes within the receptor is described. It is then shown how the flexible structures produced by this process can be rigidified by the addition of suitable ring templates.
A method is then illustrated for the conversion of molecular skeletons to synthetically accessible molecules by the replacement of ring templates, and specific substructural targets, with appropriate heteroatomic replacement fragments.
Finally the application of these techniques to a range of test systems is described.
University of Southampton
1996
Kilvington, Simon Robert
(1996)
The application of computational techniques in molecular design.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
An integrated series of techniques is described that allows the automatic construction of a diverse set of chemically reasonable and synthetically accessible molecules that are complementary to a given receptor model.
A general approach to characterising receptor targets in terms of excluded volumes and interaction sites is described that allows a variety of different systems, such as pharmacophores, enzyme active sites, signal receptors etc., to be modelled.
It is shown how novel molecules can be produced by initially constructing molecular skeletons that connect the functional groups, or larger molecular fragments, that characterise the interaction sites within the receptor model. Molecular skeletons can be built from a generic atom type, with a carbon geometry, in a two stage process. First an algorithm for linking separate molecular fragments with low energy acyclic chains that avoid the excluded volumes within the receptor is described. It is then shown how the flexible structures produced by this process can be rigidified by the addition of suitable ring templates.
A method is then illustrated for the conversion of molecular skeletons to synthetically accessible molecules by the replacement of ring templates, and specific substructural targets, with appropriate heteroatomic replacement fragments.
Finally the application of these techniques to a range of test systems is described.
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Published date: 1996
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Local EPrints ID: 460181
URI: http://eprints.soton.ac.uk/id/eprint/460181
PURE UUID: 214e2d75-2c0e-4942-add3-b43f9a54d83c
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Date deposited: 04 Jul 2022 18:06
Last modified: 04 Jul 2022 18:06
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Author:
Simon Robert Kilvington
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