Journal of Computer-Aided Molecular Design

, Volume 29, Issue 1, pp 79–87

In silico screening for Plasmodium falciparum enoyl-ACP reductase inhibitors

  • Steffen Lindert
  • Lorillee Tallorin
  • Quynh G. Nguyen
  • Michael D. Burkart
  • J. Andrew McCammon
Article

DOI: 10.1007/s10822-014-9806-3

Cite this article as:
Lindert, S., Tallorin, L., Nguyen, Q.G. et al. J Comput Aided Mol Des (2015) 29: 79. doi:10.1007/s10822-014-9806-3

Abstract

The need for novel therapeutics against Plasmodium falciparum is urgent due to recent emergence of multi-drug resistant malaria parasites. Since fatty acids are essential for both the liver and blood stages of the malarial parasite, targeting fatty acid biosynthesis is a promising strategy for combatting P. falciparum. We present a combined computational and experimental study to identify novel inhibitors of enoyl-acyl carrier protein reductase (PfENR) in the fatty acid biosynthesis pathway. A small-molecule database from ChemBridge was docked into three distinct PfENR crystal structures that provide multiple receptor conformations. Two different docking algorithms were used to generate a consensus score in order to rank possible small molecule hits. Our studies led to the identification of five low-micromolar pyrimidine dione inhibitors of PfENR.

Keywords

Computer-aided drug discovery Enoyl-acyl carrier protein reductase Virtual screening 

Supplementary material

10822_2014_9806_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2057 kb)

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Steffen Lindert
    • 1
    • 2
    • 3
  • Lorillee Tallorin
    • 3
  • Quynh G. Nguyen
    • 3
  • Michael D. Burkart
    • 3
  • J. Andrew McCammon
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Department of PharmacologyUniversity of California San DiegoLa JollaUSA
  2. 2.Center for Theoretical Biological PhysicsLa JollaUSA
  3. 3.Department of Chemistry and BiochemistryUniversity of California San DiegoLa JollaUSA
  4. 4.Howard Hughes Medical InstituteUniversity of California San DiegoLa JollaUSA
  5. 5.National Biomedical Computation ResourceUniversity of California San DiegoLa JollaUSA

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