PRO-LIGAND: an approach to de novo molecular design. 1. Application to the design of organic molecules

J Comput Aided Mol Des. 1995 Feb;9(1):13-32. doi: 10.1007/BF00117275.


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.

MeSH terms

  • Computer Simulation
  • Databases, Factual*
  • Drug Design*
  • Folic Acid Antagonists
  • HIV Protease Inhibitors*
  • Ligands
  • Methotrexate* / analogs & derivatives
  • Models, Molecular
  • Molecular Structure
  • Software*


  • Folic Acid Antagonists
  • HIV Protease Inhibitors
  • Ligands
  • Methotrexate