Comparative Dynamics and Drug Targeting against Multidrug Resistant Bordetella Pertussis

Abstract

The Bordetella Pertussis is a gram-negative bacterium and it belongs to the family of Alcaligenaceae. It is a causative agent of several types of infections mainly pertussis which infects human respiratory tracts. Pertussis is linked to the high degree of resistance to various class of antibiotics. The focus of the current study is to identify the potential drug target and to categorize the best drug candidate by employing subtractive proteomics approach and structure based virtual screening. Subtractive proteomics pipeline revealed that Capsular Polysaccharide Biosynthesis protein (CPS) that is a promising drug target. An AI based approach; Alpha fold was used for acquiring 3D structure of CPS. The Molecular Docking was performed against Chembridge library via GOLD software. Pharmacokinetic profiling was performed and several in-silico analysis such as ADMET and Toxicity analysis, Molecular Dynamics simulations, Radial Distribution Function and Binding Free Energy calculations were performed. The top inhibitors 10000290 and 10008002 with GOLD dock score 81 and 73 respectively, were used as promising drug candidates against CPS.