title: PRO-LIGAND: an approach to de novo molecular design. 1. Application to the design of organic molecules.
abstract: An approach to de novo molecular design, PRO-LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies--placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO-LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.
authors.affiliation: Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
authors.forename: D E
authors.initials: DE
authors.lastname: Clark
authors.forename: D
authors.initials: D
authors.lastname: Frenkel
authors.forename: S A
authors.initials: SA
authors.lastname: Levy
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
authors.forename: D R
authors.initials: DR
authors.lastname: Westhead
mesh_terms: D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D005493:Folic Acid Antagonists; D017320:HIV Protease Inhibitors; D008024:Ligands; D008727:Methotrexate / Q000031:analogs & derivatives; D008958:Models, Molecular; D015394:Molecular Structure; D012984:Software
chemical_list: D005493:Folic Acid Antagonists; D017320:HIV Protease Inhibitors; D008024:Ligands; D008727:Methotrexate