Comparative sequence- and structure-inspired drug design for PilF protein of Neisseria meningitidisReport as inadecuate




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Human Genomics

, 9:5

First Online: 19 April 2015Received: 11 February 2015Accepted: 01 April 2015

Abstract

Serogroup A of Neisseria meningitidis is the organism responsible for causing epidemic diseases in developing countries by a pilus-mediated adhesion to human brain endothelial cells. Type IV pilus assembly protein PilF associated with bacterial adhesion, aggregation, invasion, host cell signaling, surface motility, and natural transformation can be considered as a candidate for effective anti-meningococcal drug development. Since the crystal structure of PilF was not available, in the present study, it was modeled after the Z2491 strain CAM09255.1 using crystal structure of chain A of Vibrio cholerae putative Ntpase EpsE Protein Data Bank PDB ID: 1P9R and then we based this analysis on sequence comparisons and structural similarity using in silico methods and docking processes, to design a suitable inhibitor molecule. The ligand 3-{4S-5-{1R-1-cyclohexylethylamino}-4-5S-5-prop-2-en-1-yl cyclopent-1-en-1-yl-1,4-dihydro-7H-pyrrolo2,3-d pyrimidin-7-yl}-1,2-dideoxy-b-L-erythro-hex-1-en-3-ulofuranosyl binds to the protein with a binding energy of −8.10 kcal and showed a drug likeness of 0.952 with no predicted health hazard. It can be utilized as a potent inhibitor of N. meningitidis pilus-mediated adhesion to human brain endothelial cells preventing meningeal colonization.

KeywordsType IV pilus assembly protein PilF Homology modeling In silico drug designing Molecular docking ADME analysis Abijeet Singh Mehta and Kirti Snigdha contributed equally to this work.

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Author: Abijeet Singh Mehta - Kirti Snigdha - M Sharada Potukuchi - Panagiotis A Tsonis

Source: https://link.springer.com/



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