Computational combinatorial chemistry for de novo ligand design: Review and assessment

TitleComputational combinatorial chemistry for de novo ligand design: Review and assessment
Publication TypeJournal Article
Year of Publication1995
AuthorsCaflisch A., Karplus M.
JournalPerspectives in Drug Discovery and Design
Volume3
Issue1
Pagination51-84
Type of ArticleReview Article
ISSN0928-2866
Abstract

Computational combinatorial chemistry divides the ligand design problem into three parts: the search for optimal positions and orientations of functional groups in the binding site, the connection of such optimally placed fragments to form candidate ligands, and the estimation of their binding constants. In this review, approaches to each of these problems are described. The present limitations of methodologies are indicated and efforts to improve them are outlined. Applications to HIV-1 aspartic proteinase, which is a target for the development of AIDS therapeutic agents, and human thrombin, a multifunctional enzyme that has a central role in both haemostasis and thrombosis, are presented. The relation between combinatorial methods for drug discovery on the computer and in the laboratory is addressed.

URLhttp://dx.doi.org/10.1007/BF02174467
DOI10.1007/BF02174467
pubindex

0008

Alternate JournalPerspect. Drug Discovery Des.