Studies on the binding and interaction of neolactotetraosylceramide and peptides with dengue virus type 2 envelope protein / Asfarina Amir Hassan
Dengue fever is a common tropical infection and this acute febrile illness can be a deadly infection in cases of severe manifestation, causing dengue haemorrhagic shock syndrome. Due to the nature of the mosquito-borne infection, dengue has become a significant public health threat in many dev...
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| Format: | Thesis |
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2019
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| Online Access: | http://studentsrepo.um.edu.my/13685/ http://studentsrepo.um.edu.my/13685/4/asfarina.pdf |
| Summary: | Dengue fever is a common tropical infection and this acute febrile illness can be a
deadly infection in cases of severe manifestation, causing dengue haemorrhagic shock
syndrome. Due to the nature of the mosquito-borne infection, dengue has become a
significant public health threat in many developing tropical countries. In this study,
envelope (E) protein is selected as a target for drug design because it is believed to be
responsible for the initial viral attachment to target cells and for mediating cellular entry
of the virus. Domain III of the E-protein is found to be critical for virus adsorption to
the receptors expressed on the host cell surface. In the present work, the ability of
potential inhibitors to inhibit DENV was assessed in silico through docking of ligands
into the 1OKE pdb structure, followed by binding modes analysis and calculations of
the free energy of binding. The ligands involved were neolactotetraosylceramide
(nLc4Cer) and peptides (19-28 amino acids) that were believed to inhibit the trimeric
conformation formation of DENV E-protein. The E-protein-nLc4Cer and peptide E�protein complex models were generated using AutoDock 4.2 and Swarmdock docking
programs. Then, the interaction of complexes were analysed using molecular dynamics
simulation, followed by evaluation of the binding free energy and per-residue free
energy decomposition analysis using the Molecular Mechanics Poisson Boltzmann
Surface Area (MMPBSA) and Molecular Mechanics Generalized Born Surface Area
(MMGBSA). The amino acid residues in the DENV E-protein important for the
interactions with inhibitors had also been highlighted. These computational studies
suggest that nLc4Cer and the peptides involved are proposed as potential inhibitors of
DENV E-protein and are feasible to be developed as antiviral drugs for the treatment of
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dengue fever. The information gathered may pave the way for the design of new anti�dengue drugs thereby aiding the discovery of a therapeutic cure for this infectious
disease.
Keywords: dengue, peptide, envelope protein, molecular dynamics simulation, free
energy of binding
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