Molecular modeling, dynamics studies and virtual screening of Fructose 1, 6 biphosphate aldolase-II in community acquired- methicillin resistant <i>Staphylococcus aureus</i> (CA-MRSA)

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Title	*Molecular modeling, dynamics studies and virtual screening of Fructose 1, 6 biphosphate aldolase-II in community acquired- methicillin resistant Staphylococcus aureus* (CA-MRSA)**
Authors	Pramod Kumar Yadav¹*, Gurmit Singh², Budhayash Gautam¹, Satendra Singh¹, Madhu Yadav¹, Upasana Srivastav¹ & Brijendra Singh³
Affiliation	¹Department of Computational Biology & Bioinformatics, Sam Higginbottom Institute of Agriculture, Technology & Sciences (Deemed University), Allahabad-211007, India; ²Department of Computer Science & IT, Sam Higginbottom Institute of Agriculture, Technology & Sciences (Deemed University), Allahabad-211007, India; 3Department of Bioinformatics, CSJM University, Kanpur-208024, India.
Email	pramod.yadav@shiats.edu.in; *Corresponding author
Article Type	Hypothesis
Date	Received January 11, 2013; Accepted January 15, 2013; Published February 06, 2013
Abstract	Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as a nosocomial pathogen to the community which commonly causes skin and soft-tissue infections (SSTIs). This strain (MW2) has now become resistant to the most of the beta-lactam antibiotics; therefore it is the urgent need to identify the novel drug targets. Recently fructose 1,6 biphosphate aldolase-II (FBA) has been identified as potential drug target in CA-MRSA. The FBA catalyses the retro-ketolic cleavage of fructose-1,6-bisphosphate (FBP) to yield dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) in glycolytic pathway. In the present research work the 3D structure of FBA was predicted using the homology modeling method followed by validation. The molecular dynamics simulation (MDS) of the predicted model was carried out using the 2000 ps time scale and 1000000 steps. The MDS results suggest that the modeled structure is stable. The predicted model of FBA was used for virtual screening against the NCI diversity subset-II ligand databases which contain 1364 compounds. Based on the docking energy scores, it was found that top four ligands i.e. ZINC01690699, ZINC13154304, ZINC29590257 and ZINC29590259 were having lower energy scores which reveal higher binding affinity towards the active site of FBA. These ligands might act as potent inhibitors for the FBA so that the menace of antimicrobial resistance in CA-MRSA can be conquered. However, pharmacological studies are required to confirm the inhibitory activity of these ligands against the FBA in CA-MRSA.
Keywords	Fructose biphosphate aldolase, CA-MRSA, Modeling, Molecular dynamics simulation, Docking, Virtual screening.
Citation	Yadavet al. Bioinformation 9(3): 158-164 (2013)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.