Topics: Protein, Protein structure, Amino acid Pages: 21 (4212 words) Published: June 4, 2014
Nonylphenol and bisphenol A binding studies with antioxidant enzymes through homology modeling and molecular docking methods

M. Jayakanthan1#, R. Jubendradass2, Shereen Cynthia D’Cruz2, P. P. Mathur1,2,3*

1 Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry- 605 014, India 2 Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry - 605 014, India 3 KIIT University, Bhubaneswar - 751024, India

#Current address:
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500 007, Andhra Pradesh, India

* Corresponding author
Tel.: +91-674-2725171
Fax: +91-674-2725453

Key words: Nonylphenol; Bisphenol A; antioxidant; homology modeling; molecular docking

Bisphenol A (BPA) and nonylphenol (NP) are phenolic compounds used widely by the industries. BPA and NP are endocrine disruptors possessing estrogenic properties. Several studies have reported that BPA and NP induce oxidative stress in various organs or cell types in animals, by inhibiting the activities of antioxidant enzymes like catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. However, it is not understood how BPA and NP interact with these enzymes and inhibit their functions. Hence, it would be significant to check, whether binding sites are available for NP and BPA in antioxidant enzymes. In the present study three-dimensional structures of antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase were modeled and docked with BPA and NP. Molecular docking studies revealed that BPA and NP have binding pockets in the antioxidant enzymes. Among the antioxidant enzymes, Catalase was maximally inhibited by BPA and superoxide was maximally inhibited by NP.

1. Introduction
Molecular docking is an automated computational technique employed in computer-aided drug design for identification of potent bioactive agents. It operates by identifying the best binding mode of given ligand with its macromolecular target and evaluates the binding affinity, results of which were used in the ranking the best interacting ligands and in selection of promising bioactive compounds. Success of a molecular docking algorithm depends on the implication of efficient search method, which is used for exploring the potential energy landscape of ligands for finding their optimum configuration, accompanied with the proper scoring scheme for evaluating the binding modes of the ligand with their targets. In rigid docking methods, search algorithm employs the rotation and translational functions to locate low energy configurations, while in flexible docking methodology, sampling of various conformations of ligand is performed by altering their torsion angles. Besides, the concept of flexibility is also applied in a method called induced fit docking for searching the possible best interacting conformations of amino acids. Molecular docking is widely used for screening the libraries of compounds, for selection of best interacting hits, and in the design of novel leads based on the available drug molecules (1,2).

In the recent years, there has been much concern regarding the adverse effects of various environmental contaminants on human health. With the advent of industrialization, economic development and urbanization drastic changes occurred in the lifestyle and surroundings of humans, which resulted in the extensive production, and use of substances that could facilitate life. As a result, many potentially hazardous chemicals got released into the environment at an alarming rate and exposure to these chemicals has become inevitable. These chemicals released into the environment turned out to be one of the leading causative factors for the high incidence of various pathological conditions (3,4). Of various...

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