Molecular Docking and Simulation Study to Identify Novel Potent Inhibitors Against FmtA in Staphylococcus Aureus

Posted: 4 Feb 2020

See all articles by Vishakha Singh

Vishakha Singh

Indian Institute of Technology (IIT), Roorkee

Vikram Dalal

Indian Institute of Technology (IIT), Roorkee

Poonam Dhankhar

Indian Institute of Technology (IIT), Roorkee

Dasantila Golemi Kotra

York University

Pravindra Kumar

Indian Institute of Technology (IIT), Roorkee

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

Suggested Citation

Singh, Vishakha and Dalal, Vikram and Dhankhar, Poonam and Kotra, Dasantila Golemi and Kumar, Pravindra, Molecular Docking and Simulation Study to Identify Novel Potent Inhibitors Against FmtA in Staphylococcus Aureus (January 31, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3529035

Vishakha Singh (Contact Author)

Indian Institute of Technology (IIT), Roorkee ( email )

Department of Biotechnology
Roorkee
Roorkee, Uttarakhand 247667
India

Vikram Dalal

Indian Institute of Technology (IIT), Roorkee ( email )

DOMS
Indian Institute of Technology Roorkee
Roorkee
India

Poonam Dhankhar

Indian Institute of Technology (IIT), Roorkee ( email )

DOMS
Indian Institute of Technology Roorkee
Roorkee
India

Dasantila Golemi Kotra

York University ( email )

4700 Keele Street
Toronto, Ontario M3J 1P3
Canada

Pravindra Kumar

Indian Institute of Technology (IIT), Roorkee ( email )

DOMS
Indian Institute of Technology Roorkee
Roorkee
India

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