Screening of potent antibacterial agents targeting Clostridium difficile virulence factor toxin B: an in silico approach
Toxin B is the key determinant of virulence in Clostridium difficile. Cysteine protease domain (CPD) of toxin B plays a crucial role in host cell intoxication thereby making it a potential target for drug discovery. The present study is aimed at identifying the promising lead compounds targeting C. difficile toxin B CPD. Initial screening of the compounds was done using topomer search and drug-likeness properties. The subsequent molecular docking study yielded a set of lead compounds having better docking score and binding mode of interactions compared to the known inhibitor. Molecular dynamics simulations were performed to explore the stability of protein–ligand complexes. The identified promising lead molecules can be used for the development of therapeutics targeting C. difficile toxin B.
KeywordsHuman pathogen Therapeutic target Topomer search Drug-likeness Docking MD simulation
The author V.E. is grateful to Pondicherry University, India, for the pre-doctoral fellowship and A.J. is thankful to the University Grant Commission (UGC), New Delhi, Govt. of India, for providing research fellowship. Authors are grateful to A. Murali, Pondicherry University, Pondicherry, India and Aditya Sharma, Department of Genetics, University of Delhi, South Campus, New Delhi, India for critical reading of the manuscript and providing valuable suggestions. Authors are also thankful to Kannan M., Pondicherry University, Pondicherry, for his valuable suggestions to analysis ‘conformational changes in protein during MD simulation’.
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