Validating the role of Gram-negative bacterial Wzi as a water conduction porin and development of a tool to estimate/characterize water conduction property

Palur, Venkata Raghuvamsi (2017) Validating the role of Gram-negative bacterial Wzi as a water conduction porin and development of a tool to estimate/characterize water conduction property. Masters thesis, Indian Insitute of Technology Hyderabad.

Text
BO15MTECH11002.pdf - Submitted Version
Restricted to Registered users only until 5 July 2020.
Download (3MB) | Request a copy

Abstract

Antimicrobial resistance (AMR) is a major threat to human health. Multiple studies have shown many bacterial species have developed resistance to major and common antibiotics. It is extremely necessary to explore and validate novel drug targets to design next generation of drug which target bacterial virulence. One such major component of bacterial virulence factor is capsular polysaccharide (CPS) which functions as a mask to evade host immune response and also acts as a barrier for antibiotics. Targeting key components in Wzy dependent CPS biosynthesis and exportation pathway could prove to be valuable drug target as major Gram-negative pathogenic bacteria like Escherichia coli, Klebsiella pneumoniae & Acinetobacter baumanii employ Wzy dependent pathway. Among seven proteins involved in Wzy pathway, Wzi a outer membrane protein having a dual role as lectin and a water conducting porin, could be a potential drug target. Thus, it is necessary to elucidate the molecular details in functioning of Wzi to exploit it as drug target. Hence, homologs of E.coli Wzi from Klebsiella pneumoniae, Acinetobacter baumanii and Pseudoaltromonas atlantica are modeled to carry out molecular dynamics (MD) simulation to elucidate common and critical aspects in water conduction property. Purification protocol of Wzi is also standardized so as to facilitate the corroboration of water conduction property. Further, a tool has been developed to characterize the water conduction property of Wzi from MD trajectories. This tool can be employed to characterize the solvent conduction in any protein channel.

[error in script]

IITH Creators: