Next Article in Journal
Substrate Temperature Dependent Surface Morphology and Photoluminescence of Germanium Quantum Dots Grown by Radio Frequency Magnetron Sputtering
Previous Article in Journal
Theoretical Models for Surface Forces and Adhesion and Their Measurement Using Atomic Force Microscopy
Previous Article in Special Issue
Proteins of Unknown Function in the Protein Data Bank (PDB): An Inventory of True Uncharacterized Proteins and Computational Tools for Their Analysis
Article Menu

Export Article

Open AccessReview
Int. J. Mol. Sci. 2012, 13(10), 12857-12879; doi:10.3390/ijms131012857

Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls

School of Chemistry, University of Wollongong, Northfields Ave, Wollongong 2522, NSW, Australia
*
Author to whom correspondence should be addressed.
Received: 4 July 2012 / Revised: 30 August 2012 / Accepted: 19 September 2012 / Published: 8 October 2012
(This article belongs to the Special Issue Protein Crystallography in Molecular Biology)
View Full-Text   |   Download PDF [802 KB, uploaded 19 June 2014]   |  

Abstract

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality. View Full-Text
Keywords: fragment-based screening; crystallography; drug design; synchrotron radiation; X-ray fragment-based screening; crystallography; drug design; synchrotron radiation; X-ray
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Chilingaryan, Z.; Yin, Z.; Oakley, A.J. Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls. Int. J. Mol. Sci. 2012, 13, 12857-12879.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top