Library screening by fragment-based docking

TitleLibrary screening by fragment-based docking
Publication TypeJournal Article
Year of Publication2010
AuthorsHuang D., Caflisch A.
JournalJournal of Molecular Recognition
Volume23
Issue2
Pagination183-193
Date Published2010 Mar-Apr
Type of ArticleReview Article
ISSN1099-1352
KeywordsAmyloid Precursor Protein Secretases, Cathepsin B, Cyclin-Dependent Kinase 2, Enzyme Inhibitors, Enzymes, High-Throughput Screening Assays, Humans, Models, Molecular, Molecular Structure, Peptide Fragments, Peptide Library, Protein Conformation, Protozoan Proteins, Receptor, EphB4, RNA Helicases, Serine Endopeptidases, Viral Nonstructural Proteins
Abstract

We review our computational tools for high-throughput screening by fragment-based docking of large collections of small molecules. Applications to six different enzymes, four proteases, and two protein kinases, are presented. Remarkably, several low-micromolar inhibitors were discovered in each of the high-throughput docking campaigns. Probable reasons for the lack of submicromolar inhibitors are the tiny fraction of chemical space covered by the libraries of available compounds, as well as the approximations in the methods employed for scoring, and the use of a rigid conformation of the target protein.

DOI10.1002/jmr.981
pubindex

0126

Alternate JournalJ. Mol. Recognit.
PubMed ID19718684
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