Volume 4 Supplement 1
Development of target focused library against drug target of P. falciparumusing SVM and Molecular docking
© Subramaniam et al; licensee BioMed Central Ltd. 2012
Published: 1 May 2012
PfHslV, a homolog of β subunit of 20S proteasome forms the proteolytic core of the PfHslUV machinery in P. falciparum [1, 2]. PfHslV has no homolog in the human host and it is a promising drug target essential to the plasmodial metabolism. The use of single proteasome inhibitor targeting these threonine proteases has a potential to be antimalarial drug candidate. One of our recent studies identified several promising inhibitors against 20S β5 subunit of P. falciparum . The present study adopts a similar knowledge based virtual screening strategy using Support Vector Machines (SVM) and molecular docking to build a focused library of potential PfHslV inhibitors. SVM model has been trained using 170 molecular descriptors of 64 inhibitors and 208 putative non-inhibitors. The non-linear classifier based on Radial Basis Function (RBF) kernel yielded classification accuracy of 97%. The SVM model rapidly predicted inhibitors from NCI library and were subsequently docked in to the active site of an optimised three-dimensional model of PfHslV. The novel drug-like PfHslV inhibitors with very good binding affinity and novel scaffold can be a good starting point to develop new antimalarial drugs.
- Ramasamy G, Gupta D, Mohmmed A, Chauhan VS: Characterization and localization of Plasmodium falciparum homolog of prokaryotic ClpQ/HslV protease. Mol Biochem Parasitol. 2007, 152: 139-148. 10.1016/j.molbiopara.2007.01.002.View ArticleGoogle Scholar
- Subramaniam S, Mohmmed A, Gupta D: Molecular modeling studies of the interaction between Plasmodium falciparum HslU and HslV Subunits. J Biomol Struct Dyn. 2009, 26: 403-524.View ArticleGoogle Scholar
- Subramaniam S, Mehrotra M, Gupta D: Support Vector Machine based prediction of P. falciparum proteasome inhibitors and development of focused library by molecular docking. Comb Chem High Throughput Screen. 2011, 14 (10): 898-907. 10.2174/138620711797537058.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.