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An in silico structure-based approach to anti-infective drug discovery

Published online by Cambridge University Press:  17 June 2013

FRASER CUNNINGHAM ,
MARTIN J. McPHILLIE ,
A. PETER JOHNSON  and
COLIN W. G. FISHWICK
FRASER CUNNINGHAM
Affiliation:
School of Chemistry, University of Leeds, Leeds, UK
MARTIN J. McPHILLIE
Affiliation:
School of Chemistry, University of Leeds, Leeds, UK
A. PETER JOHNSON
Affiliation:
School of Chemistry, University of Leeds, Leeds, UK
COLIN W. G. FISHWICK*
Affiliation:
School of Chemistry, University of Leeds, Leeds, UK
*
*Corresponding author. School of Chemistry, University of Leeds, Leeds, UK. Tel: +44 (0)113 3436510. Fax: +44 (0) 113 343 6565 E-mail: C.W.G.Fishwick@leeds.ac.uk
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Summary

In light of the low success rate of target-based genomics and HTS (High Throughput Screening) approaches in anti-infective drug discovery, in silico structure-based drug design (SBDD) is becoming increasingly prominent at the forefront of drug discovery. In silico SBDD can be used to identify novel enzyme inhibitors rapidly, where the strength of this approach lies with its ability to model and predict the outcome of protein-ligand binding. Over the past 10 years, our group have applied this approach to a diverse number of anti-infective drug targets ranging from bacterial D-ala-D-ala ligase to Plasmodium falciparum DHODH. Our search for new inhibitors has produced lead compounds with both enzyme and whole-cell activity with established on-target mode of action. This has been achieved with greater speed and efficiency compared with the more traditional HTS initiatives and at significantly reduced cost and manpower.

Keywords

in silico drug discoverymalariaDHODHbacterial resistanceRNA polymeraseD-ala-D-ala ligase
Type
Research Article
Information
Parasitology , Volume 141 , Issue 1: Symposia of the British Society for Parasitology volume 49 Emerging paradigms in anti-infective drug design , January 2014 , pp. 17 - 27
Copyright
Copyright © Cambridge University Press 2013 

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