Exploring QSTR modeling and toxicophore mapping for identification of important molecular features contributing to the chemical toxicity in Escherichia coli Subrata Pramanik 1 , Kunal Roy ⇑,1 Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India article info Article history: Received 17 June 2013 Accepted 4 November 2013 Available online 15 November 2013 Keywords: Biodiversity Escherichia coli QSTR Chemical toxicity Statistical modeling Toxicophore abstract Biodiversity deprivation can affect functions and services of the ecosystem. Changes in biodiversity alter ecosystem processes and change the resilience of ecosystems to ecological changes. Bacterial communi- ties are the main form of biomass in the ecosystem and one of largest populations on the planet. Bacterial communities provide important services to biodiversity. They break down pollutants, municipal waste and ingested food, and they are the primary route for recycling of organic matter to plants and other autotrophs, conversion of inorganic matter into new biological tissue using sunlight, management of energy crisis through use of biofuel. In the present study, computational chemistry and statistical mod- eling have been used to develop mathematical equations which can be applied to calculate toxicity of new/unknown chemicals/biofuels/metabolites in Escherichia coli. 2D and 3D descriptors were generated from molecular structure of compounds and mathematical models have been developed using genetic function approximation followed by multiple linear regression (GFA-MLR) method. Model validity was checked through defined internal (R 2 = 0.751 and Q 2 = 0.711), and external (R 2 pred ¼ 0:773) statistical parameters. Molecular features responsible for toxicity were also assessed through 3D toxicophore study. The toxicophore-based model was validated (R = 0.785) using qualitative statistical metrics and random- ization test (Fischer validation). Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction The most unique feature of Earth for being the major Planet is the existence of life, and the most extraordinary feature of life is its diversity (Cardinale et al., 2012). Loss of biodiversity can affect ecosystem functions and services (Loreau et al., 2001, 2002; Kinzig et al., 2002; Hooper et al., 2005; Hector and Bagchi, 2007). These changes in biodiversity alter ecosystem processes and change the resilience of ecosystems to ecological changes (Chapin III et al., 2000; Venail et al., 2008). As the growing civilization is facing a huge crisis in industrial chemicals, food and energy, production of medicinal agents, agro- chemicals and biofuel need engineered microorganisms through biotechnological approaches. The use of multivariate-modular ap- proach of engineering metabolic-pathway for designing and man- ufacturing of various important plant and animal secondary metabolites, genomics and proteomics needs alteration of cellular signaling pathways (Anthony et al., 2009; Edwards and Palsson, 2000; Planson et al., 2012). The increasing production and use of such bioengineered products and genetic manipulation have led to concerns about their possible impact on microbes in the envi- ronment (Gent, 1999). Industrial chemicals, biofuels, bioengineered products and wastes are disposed into the ecosystem despite their toxicity po- tential (Planson et al., 2012; Zaldivar and Ingram, 1999; Lozano et al., 2010). As biotechnology industries start to come on line of massive production, it is also unavoidable to escape the entrance of these products and their by-products in the ecosystem and their effect on microbes in the ecosystem (Dunlop et al., 2011). There- fore, any factors that may affect the microbial ecology are being looked for using multidimensional approach in environmental research. In the last few decades a large number of in silico, in vitro and in vivo research studies have been carried out on diverse chemicals using mainly eukaryotic cells (Valerio, 2009). However, to the best of our knowledge, relatively a few in silico studies have been dealt with the direct or indirect toxicity of bioengineered products on prokaryotic cells such as Escherichia coli (Planson et al., 2012). 0887-2333/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tiv.2013.11.002 ⇑ Corresponding author. Present address: Manchester Institute of Biotechnology, Manchester M1 7DN, United Kingdom. E-mail addresses: kunalroy_in@yahoo.com, kroy@pharma.jdvu.ac.in, kunal.- roy@manchester.ac.uk (K. Roy). URL: http://sites.google.com/site/kunalroyindia/ (K. Roy). 1 Tel.: +91 98315 94140, +44 7579206865; fax: +91 33 2837 1078. Toxicology in Vitro 28 (2014) 265–272 Contents lists available at ScienceDirect Toxicology in Vitro journal homepage: www.elsevier.com/locate/toxinvit