Drug Repurposing against Anhydro-N-acetylmuramic Acid Kinase of Multi-Drug Resistant Acinetobacter baumannii: An in Silico Approach

Debdoot Gupta^* and Priya Mondal

Department of Microbiology, The University of Burdwan, Burdwan, India.

Corresponding Author E-mail:dgupta@microbio.buruniv.ac.in

DOI : http://dx.doi.org/10.13005/bbra/3184

ABSTRACT: Acinetobacter baumannii, a gram-negative coccobacillus is accountable for different nosocomial diseases. It has been enlisted in the ‘critical’ category in WHO published list depending on the urgency for novel drug development as it becomes multidrug resistant (MDR). The aim of this study was to find a drug which can be repurposed against any drug target of these bacteria and thus the time and cost required for typical drug development procedure can be bypassed. In this study, Anhydro-N-acetylmuramic acid kinase (AnmK) of Acinetobacter baumannii was analyzed to be a good drug target which is responsible for the structural integrity of the cell wall of these bacteria. The expression probability of the protein is high with 0.916. PROTPARAM analysis shows that it is a thermostable, non polar protein with molecular weight of 41.7 kDa and pI in the acidic range. The structure prediction was done with SWISS-MODEL (with 46.71% identity with the template) and was found reliable with 91.8% amino acid in allowable region. This predicted structure was used for dug repurposing in which drugs are screened from ZINC15 database (containing FDA approved drug) to find their effective binding (if any) with this protein. PyRx software was used for the docking process which found Ergotamine as the most promising repurposed drug in terms of binding energy(-10.5 kcal/mole) and vina score(-10.3 kcal/mole). Molecular Dynamics Simulation shows that binding of this drug with the protein target is stable over picoseconds time scale.

KEYWORDS: Anhydro-N-acetylmuramic acid kinase; Drug repurposing; MDR; PROTPARAM; PyRx; ZINC15

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