PRO-LIGAND: an approach to de novo molecular design. 1. Application to the design of organic molecules.
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.
Clark
D E
DE
Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
Frenkel
D
D
Levy
S A
SA
Li
J
J
Murray
C W
CW
Robson
B
B
Waszkowycz
B
B
Westhead
D R
DR
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
D005493:Folic Acid Antagonists; D017320:HIV Protease Inhibitors; D008024:Ligands; D008727:Methotrexate