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In search of the representative pharmacophore hypotheses of the enzymatic proteome of Plasmodium falciparum: a multicomplex-based approach

  • Anu Manhas
  • Mohsin Y. Lone
  • Prakash C. Jha
Short Communication
  • 16 Downloads

Abstract

Drug resistance has made malaria an untreatable disease and therefore intensified the need for the development of new drugs and the identification of potential drug targets. In this pursuit, in silico efforts made in the past have not shown significant responses. Therefore, in the present work, the multicomplex-based pharmacophore modeling approach was employed to construct the pharmacophores of the 16 selected Plasmodium falciparum (Pf) targets. All the constructed hypotheses (153) were screened against a focused dataset made up of experimental actives of the chosen targets (3705 inhibitors). The rationale was to check the affinity of the inhibitors for the off-targets. Subsequently, the constructed hypotheses from each target were pooled based on the feature types and the pooled-hypotheses were then clustered to offer an insight about the pharmacophore similarity. Tanimoto similarity index was also calculated to look for the similarity among the inhibitors belonging to different Pf targets. Overall, the work was accomplished to bid healthier perceptive of the pharmacophore-based virtual screening and abet in providing guiding principles for the construction of stringent pharmacophores that can be employed for the screening.

Graphical abstract

Keywords

Multicomplex-based pharmacophore Enzymatic proteome Clustering Tanimoto similarity Virtual screening 

Notes

Acknowledgements

Anu Manhas and PCJ acknowledge Science and Engineering Research Board (SERB), Department of Science and Technology (DST) for project grant through grant number EMR/2016/003025. MY Lone acknowledges the University Grants Commission (UGC), Govt. of India for the financial assistance.

Compliance with ethical standards

Conflict of interest

The authors declared no competing interest.

Supplementary material

11030_2018_9885_MOESM1_ESM.docx (4.9 mb)
Supplementary material 1 (DOCX 5066 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.School of Chemical SciencesCentral University of GujaratGandhinagarIndia
  2. 2.Department of ChemistryIndian Institute of Technology GandhinagarGandhinagarIndia
  3. 3.Centre for Applied ChemistryCentral University of GujaratGandhinagarIndia

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