Molecular Docking and Simulation Study to Identify Novel Potent Inhibitors Against FmtA in Staphylococcus Aureus
Posted: 4 Feb 2020
Date Written: January 31, 2020
Abstract
Staphylococcus aureus is a gram-positive bacterium causing pneumonia, endocarditis and sepsis. Screening for Staphylococcus aureus has resulted in the identification of auxillary genes like fmtA, llm, and other factors. FmtA possess novel hydrolytic activity toward the ester bond between D-Ala and the backbone of teichoic acids (TAs). TAs are polyol-phosphate polymers found in the Staphylococcus aureus cell wall that play important roles in antibiotic resistance and pathogenesis. Two of the PRPs conserved motifs, namely SXXK and Y(S)XN, are involved in the hydrolysis by FmtA, but its catalytic mechanism remains elusive. In the present study, we determined the crystal structure and identified the potent inhibitors that can effectively bind to FmtA. We screened active compounds and the binding affinity was confirmed using molecular docking study. The enzyme-ligand complex which showed higher binding affinity than substrate was employed for subsequent analysis. Molecular dynamics studies were utilized to validate the dynamics and stability of top scoring protein-inhibitor complex using GROMACS 5.1.4. Molecular dynamics revealed a similar pattern of deviation, fluctuation, and compactness in the protein-inhibitor complex as compared to the protein-substrate complex. Further, in-vitro binding assays will be performed to check the inhibition of novel esterase for the inhibition of Staphylococcus aureus.
Keywords: Staphylococcus aureus,FmtA,Molecular Dynamics,Penicillin recognizing proteins
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