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Homology modeling and molecular dynamics simulation of N-myristoyltransferase from Plasmodium falciparum: an insight into novel antimalarial drug design

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Abstract

Malaria is an infectious disease caused by parasites of the genus Plasmodium. It leads to approximately 1 million deaths per annum worldwide, with an increase number of 6.27 million deaths in 2012 alone. Validation of new antimalarial targets is very important in the context of the rise in resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase (NMT), which catalyzes the attachment of the fatty acid myristate to protein substrates (N-myristoylation) for activation. Reports suggests that NMT is an essential and chemically docile target in malaria parasites both in vitro and in vivo, and the selective inhibition of N-myristoylation leads to irreversible failure to form an inner membrane complex—an essential subcellular organelle in the parasite life cycle. In this work, we modeled the three-dimensional structure of Plasmodium falciparum NMT (PfNMT) using Modeler 9.0 taking Plasmodium vivax NMT (PvNMT) as the template. The novelty of the work lies in the selection of template as the similarity of PfNMT with PvNMT was 80.47 %, whereas earlier similar work showed template similarity with Candida albicans NMT (CaNMT) and Saccharomyces cerevisiae NMT (ScNMT) to be less than 50 %. The generated structure was then validated using various programs such as PROCHECK, RAMPAGE server, CHIMERA and the stability of the model was checked by Gromacs 5.0.

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Acknowledgments

The authors acknowledge the support of Bioinformatics Center (DBT-BIF), Assam University, Silchar for use of computational tools and the DBT e-Library Consortium (DeLCON) facility for literature search. The corresponding author, A. Chowdhury is in receipt of fellowship from DBT sponsored Biotech Hub, Assam University, Silchar.

Conflict of interest

The authors declare no conflict of interest. The authors follow Ministry of Science & Technology, Govt. of India Open Access Policy.

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Authors and Affiliations

  1. Bioinformatics Centre, Assam University, Silchar, Assam, 788011, India

    Paulomi Paul, Abhishek Chowdhury, Anupam Das Talukdar & Manabendra Dutta Choudhury

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  1. Paulomi Paul
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  2. Abhishek Chowdhury
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  3. Anupam Das Talukdar
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  4. Manabendra Dutta Choudhury
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Correspondence to Abhishek Chowdhury.

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Paul, P., Chowdhury, A., Talukdar, A.D. et al. Homology modeling and molecular dynamics simulation of N-myristoyltransferase from Plasmodium falciparum: an insight into novel antimalarial drug design. J Mol Model 21, 37 (2015). https://doi.org/10.1007/s00894-015-2586-4

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  • DOI: https://doi.org/10.1007/s00894-015-2586-4

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