1 Department of Bioinformatics, Computer Aided Drug Design and Molecular Modelling Lab, Science Block, Alagappa University, Karaikudi, Tamil Nadu, India.
2 Centre for Research in Molecular Modelling, Concordia University, 5618 Montreal, Quebec, Canada.
3 Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia.
4 Department of Microbiology and Immunology, Veterinary Research Division, National Research Center (NRC), Giza, Egypt.
5 Department of Biology, College of Science in Zulfi, Majmaah University, Majmaah 11952, Saudi Arabia.
6 Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
7 Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Bacillus anthracis is a gram positive, deadly spore forming bacteria causing anthrax and these bacteria having the complex mechanism in the cell wall envelope, which can adopt the changes in environmental conditions. In this, the membrane bound cell wall proteins are said to progressive drug target for the inhibition of Bacillus anthracis. Among the cell wall proteins, the SrtA is one of the important mechanistic protein, which mediate the ligation with LPXTG motif by forming the amide bonds. The SrtA plays the vital role in cell signalling, cell wall formation, and biofilm formations. Inhibition of SrtA leads to rupture of the cell wall and biofilm formation, and that leads to inhibition of Bacillus anthracis and thus, SrtA is core important enzyme to study the inhibition mechanism. In this study, we have examined 28 compounds, which have the inhibitory activity against the Bacillus anthracis SrtA for developing the 3D-QSAR and also, compounds binding selectivity with both open and closed SrtA conformations, obtained from 100 ns of MD simulations. The binding site loop deviate in forming the open and closed gate mechanism is investigated to understand the inhibitory profile of reported compounds, and results show the closed state active site conformations are required for ligand binding specificity. Overall, the present study may offer an opportunity for better understanding of the mechanism of action and can be aided to further designing of a novel and highly potent SrtA inhibitors.