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Volume 6, Issue 4 (Suppl)
Clin Pharmacol Biopharm, an open access journal
ISSN: 2167-065X
Page 71
Euro Biopharma & Ethnopharmacology 2017
November 09-11, 2017
&
6
th
International Conference and Exhibition on
November 09-11, 2017 Vienna, Austria
4
th
EUROPEAN BIOPHARMA CONGRESS
PHARMACOLOGY AND ETHNOPHARMACOLOGY
Joint Event
Structure– and ligand–guided screening of LptA inhibitors: An initial study for developing novel
Neisserial antibacterials
Abi Sofyan Ghifari
University of Western Australia, Australia
P
athogenic Gram-negative bacteria such as Neisseria meningitidis and Neisseria gonorrhoeae have developed resistance
against antibiotics due to their ability in creating an envelope on the outer layer of lipooligosaccharides (LOS). The cationic
phosphoethanolamine (PEA) decoration of LOS’ lipid A is regulated by lipid A–PEA transferase A (LptA) which may serve as a
prominent target for developing new antibiotics.The discovery of Neisserial LptA has provided a structural aspect to its catalytic
mechanisms and ligand recognition that are crucial for inhibitor development. A combination of structure– and ligand–based
approach has been employed to explore novel potent LptA inhibitors among millions of commercially-available compounds
and approved drugs. A total of 4000 hit molecules obtained from LIDAEUS structure–based screening and PubMed ligand
similarity search were further examined through semi-flexible docking simulation performed in MOE and Schrödinger’s
Glide. Best hits were therefore carefully selected based on their docking score, drug likeness, and pharmacological properties.
Free energy of binding calculation and ligand interaction analysis suggest that the selected 20 hit compounds have a stronger
binding affinity than LptA natural substrate and possess a more effective interaction with catalytically–essential residues.
Further molecular dynamics (MD) simulation of these 20 compounds also confirms that they all maintained stable complex
conformation showing low total RMSD, capability to maintain interactions with active site, and acceptable Ramachandran
plot. This study provides an insight to drug repurposing which may serve as an initial step to develop novel potent LptA
inhibitors to combat the virulence of multi-drug resistant Neisseria.
abi.ghifari@gmail.comClin Pharmacol Biopharm 2017, 6:4(Suppl)
DOI: 10.4172/2167-065X-C1-026