Membrane pore formation and ion selectivity of the Ebola virus delta peptide

Physical Chemistry Chemical Physics : PCCP
Rudramani PokhrelPrem P Chapagain

Abstract

The Ebola virus (EBOV) is a filamentous lipid-enveloped virus that causes severe hemorrhagic fever with a high fatality rate in humans. The EBOV encodes a glycoprotein that when cleaved, produces the delta peptide. Experimental evidence suggests that the delta peptide functions as a viroporin that enhances virus particle release through the host cell membrane. However, the viroporin forming mechanism of the delta peptide is still not well understood. Guided by experimental information, we have computationally investigated the pore formation by different oligomers of the delta peptide. We have performed all-atom molecular dynamics (MD) simulations in an explicit membrane environment to investigate the pore-forming mechanism and stability of the pores. Our results suggest that the delta peptide forms stable pentameric pores. In addition, the pore is selective with respect to chloride ions, and the disulfide bond formed between Cys-29 and Cys-38 in the C-terminal of the peptide is essential for the pore stabilization and ion permeation. Our study provides helpful information on the pore-forming mechanism of filovirus delta peptides and such structural information can be important in designing and developing molecular modulators th...Continue Reading

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Oct 21, 2016·Physical Chemistry Chemical Physics : PCCP·Jeevan B GcPrem P Chapagain
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Citations

May 31, 2019·Physical Chemistry Chemical Physics : PCCP·Rudramani PokhrelPrem P Chapagain
Jul 1, 2021·Biological Chemistry·Rajendra P KoiralaNarayan P Adhikari
Aug 25, 2020·Chemistry of Heterocyclic Compounds·Vadim A Shiryaev, Yuri N Klimochkin
Dec 8, 2021·Journal of Chemical Theory and Computation·Rudramani PokhrelPrem P Chapagain

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Software Mentioned

HOLE
GUI
Visual Molecular Dynamics ( VMD )
CHARMM
Phyre2
NAMD2
GPU
VMD Density Profile Tool

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