title: Molecular modeling, dynamics studies and virtual screening of Fructose 1, 6 biphosphate aldolase-II in community acquired- methicillin resistant Staphylococcus aureus (CA-MRSA).
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.
authors: Department of Computational Biology & Bioinformatics, Sam Higginbottom Institute of Agriculture, Technology & Sciences (Deemed University), Allahabad-211007, India.
authors: Pramod Kumar
authors: PK
authors: Yadav
authors: Gurmit
authors: G
authors: Singh
authors: Budhayash
authors: B
authors: Gautam
authors: Satendra
authors: S
authors: Singh
authors: Madhu
authors: M
authors: Yadav
authors: Upasana
authors: U
authors: Srivastav
authors: Brijendra
authors: B
authors: Singh
keywords: CA-MRSA; Docking; Fructose biphosphate aldolase; Modeling; Molecular dynamics simulation; Virtual screening