title: PRO-LIGAND: an approach to de novo molecular design. 3. A genetic algorithm for structure refinement.
abstract: Recently, the development of computer programs which permit the de novo design of molecular structures satisfying a set of steric and chemical constraints has become a burgeoning area of research and many operational systems have been reported in the literature. Experience with PRO-LIGAND-the de novo design methodology embodied in our in-house molecular design and simulation system PRO-METHEUS-has suggested that the addition of a genetic algorithm (GA) structure refinement procedure can 'add value' to an already useful tool. Starting with the set of designed molecules as an initial population, the GA can combine features from both high- and low-scoring structures and, over a number of generations, produce individuals of better score than any of the starting structures. This paper describes how we have implemented such a procedure and demonstrates its efficacy in improving two sets of molecules generated by different de novo design projects.
authors.affiliation: Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
authors.forename: D R
authors.initials: DR
authors.lastname: Westhead
authors.forename: D E
authors.initials: DE
authors.lastname: Clark
authors.forename: D
authors.initials: D
authors.lastname: Frenkel
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: C W
authors.initials: CW
authors.lastname: Murray
authors.forename: B
authors.initials: B
authors.lastname: Robson
authors.forename: B
authors.initials: B
authors.lastname: Waszkowycz
mesh_terms: D000465:Algorithms; D005075:Biological Evolution; D003196:Computer Graphics; D015195:Drug Design; D008727:Methotrexate / Q000737:chemistry; D008957:Models, Genetic; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D011758:Pyrroles / Q000737:chemistry; D012984:Software
chemical_list: D011758:Pyrroles; D008727:Methotrexate