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A genetic algorithm has been designed which generates molecular structures within constraints. The constraints may be any useful function, for example an enzyme active site, a pharmacophore or molecular properties from pattern recognition or rule-induction analyses. The starting point may be random or may utilise known molecules. These are modified to 'grow' into families of structures which, using the evolutionary operators of selection, crossover and mutation evolve to better fit the constraints. The basis of the algorithm is described together with some applications in lead generation, 3D database construction and drug design. Genetic algorithms of this type may have wider applications in chemistry, for example in the design and optimisation of new polymers, materials (e.g. superconducting materials) or synthetic enzymes.

Original publication

DOI

10.1007/bf00124408

Type

Journal

Journal of computer-aided molecular design

Publication Date

04/1995

Volume

9

Pages

181 - 202

Addresses

Department of Physical Sciences, Wellcome Research Laboratories, Beckenham, Kent, U.K.

Keywords

Trimethoprim, Tetrahydrofolate Dehydrogenase, Ribose, Binding Sites, Molecular Conformation, Protein Conformation, Hydrogen Bonding, Algorithms, Models, Genetic, Models, Molecular, Automation, Computer Graphics, Software