[Product Releases]

• eHiTS v9.1
• Score v9.1
• LASSO v9.1
• CheVi
• SPROUT
• ARChem
• CAESA
• CLiDE v5

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[News]

Can we trust docking results?
Sept 2010

IBM Systems and Technology Group releases a white paper with eHiTS and Cell
Oct 2008

EPA's ToxCast^TM project will use SimBioSys' eHiTS as docking engine
Nov, 2007

[Events]

243rd ACS
Mar 25-29, 2012
San Diego, CA
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Computational approaches to antibacterial and antimalarial hit
finding

A. Peter Johnson (1), Colin Fishwick (1), Glenn A. McConkey (2), Timo Heikkila (3), Matthew Davies (2), Deborah Cowan (1), and Anil Agarwal (1)

(1) School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK
(2) Faculty of Biological Sciences, University of Leeds, UK
(3) Facullty of Biological Sciences, University of Leeds, UK

Abstract:

Malaria and tuberculosis are major causes of mortality in developing countries, a situation exacerbated by the emergence of species resistant to current therapies. Structure based approaches have been applied to the design of inhibitors of the essential enzymes (a) dihydroorotate dehydrogenase from P. falciparum and (b) bacterial RNA polymerase, the target of tuberculosis therapy using analogues of rifamycin. De novo design (SPROUT) and virtual high throughput screening (eHITS) led to a series of ligand structures, a small number of which were synthesised or purchased as appropriate and subjected to biological assay which identified several low micromolecular inhibitors. Structure based hit optimisation (using SPROUT LeadOpt) provided compounds with increased inhibitory activity. The higher than usual success rate achieved in the virtual high throughput screening approach is attributed to the accuracy and conservatism of the eHITS scoring function. Details of the computational and experimental techniques and results will be presented.

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