Effective interaction studies for inhibition of DNA ligase protein from Staphylococcus aureus

Abstract

Staphylococcus aureus has been recognized as an important human pathogen for more than 100 years. It is among the most important causative agent of human infections in the twenty-first century. DNA ligase is the main protein responsible for the replication of S. aureus. In order to control the replication mechanism, DNA ligase is a successive drug target, hence we have chosen this protein for this study. We performed virtual screening using ZINC database for identification of potent inhibitor against DNA ligase. Based on the scoring methods, we have selected best five compounds from the ZINC database. In order to improve the accuracy, selected compounds were subjected into Quantum Polarized Ligand Docking (QPLD) docking, for which the results showed high docking score, compared to glide docking score. QPLD is more accurate as it includes charges in the scoring function, which was not available in the glide docking. Binding energy calculation results also indicated that selected compounds have good binding capacity with the target protein. In addition, these compounds on screening have good absorption, distribution, metabolism, excretion and toxicity property. In this study, we identified few compounds that particularly work against DNA ligase protein, having better interaction phenomenon and it would help further the experimental analysis.

• ADME
• DNA ligase
• molecular docking
• QM/MM
• Staphylococcus aureus
• virtual screening

Acknowledgements

One of the authors (P. V.) thanks C. Selvaraj and Sanjeev Kumar Singh, Alagappa University, for research support activities.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. The financial support extended by the BTIS (Biotechnology Information System), DBT (Department of Biotechnology), Ministry of Science and Technology, Government of India, is acknowledged.