Abstract

DISCOVERY OF STREPTOCOCCAL PNEUMONIA CHOLINE BINDING PROTEIN INHIBITORS USING PHARMACOPHORE MODELING AND QSAR ANALYSIS

Shilpa N*, Tanusree Bhattacharya, Anita P M and Kusum Paul

ABSTRACT

Pneumococcal disease is an infection caused by Streptococcus pneumoniae is an anaerobic gram positive bacteria and which is responsible for many types of diseases like pneumonia, ear infections, sinus infections, bacterial meningitis and bacteremia. In present era there are several virulence factors which are resisting antimicrobial agents and escapes immune defenses, these factors helps with therapeutic intervention.The capsule of this pathogenic bacterium is the major virulence factor and the synthesis of capsule is being governed by capsular polysaccharide gene clusters, which encodes for Pneumococcal choline binding regulatory proteins such as CbpA, PcsB and PcpA. Studies have suggested that activities of these choline binding proteins are therapeutic targets for several types of bacterial infections. Thus protein-targeted drug against cytoplasmic and cytosol proteins is a good alternative to protect against pneumonia. In this study we used homology modeling and validation of proteins was performed with certain bioinformatics tools, which facilitates the execution of molecular docking against the ligands which are taken from the CHEMSPIDER database. The Chemoinformatics approaches used for ligand based molecular screening to predict the Pharmacophore, pharmacokinetic and bioavailability properties that lead to improve pharmacological properties and validate based on molecular docking studies. The potential ligand molecules bind substantially in the active site of these regulatory proteins with considerable binding energy in the docking study, which means that the potential ligands could be considered as the good inhibitors. This study helps to understand the functional aspects of this and also to examine the development of a novel drug against pneumonia.

Keywords: Streptococcus pneumoniae, drug target, homology modeling, docking,