Article
Incorporating Receptor Flexibility into Structure-Based Drug Discovery
Computer-Aided Drug Discovery
(2015)
Abstract
Biological receptors are not completely rigid molecules. They can adopt many different structures at physiologically relevant temperatures. Different drugs can bind to different ensembles of conformations of these receptors. Reliably predicting to which conformations of a receptor a compound might bind well calls for the proper account of receptor flexibility. Researchers have developed various computational methods to deal with this aspect of drug discovery. Some of these methods are still too expensive to be used extensively in practice. Ensemble docking has emerged as one of the most popular practical approaches. This chapter summarizes basic principles and common techniques underlying ensemble docking, illustrates its use with several examples, and concludes with suggestions for future improvements.
Keywords
- Computer-aided drug design,
- Ensemble docking,
- Molecular dynamics,
- Normal mode,
- Conformational transition paths,
- Homology modeling,
- Virtual screening,
- Enrichment factor,
- Boltzmann-enhanced discrimination of receiver operating characteristics (BEDROC)
Disciplines
Publication Date
January 1, 2015
DOI
10.1007/7653_2015_56
Citation Information
Chung F. Wong. "Incorporating Receptor Flexibility into Structure-Based Drug Discovery" Computer-Aided Drug Discovery (2015) p. 65 - 84 Available at: http://works.bepress.com/chung-wong/12/