An all-atom molecular dynamics study of the anti-interferon signaling of Ebola virus: interaction mechanisms of EBOV VP24 binding to Karyopherin alpha5.

Ebola virus (EBOV) is highly lethal due to virally encoded immune antagonists, and the combination of EBOV VP24 with karyopherin alpha (KPNA) will trigger anti-interferon (IFN) signaling. The crystal structure of VP24-KPNA5 has been proposed in recent studies, but the precise binding mechanisms are still unclear. In order to explore the VP24-KPNA5 protein binding micro-mechanisms, Molecular Dynamic (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MM-GB/SA) energy calculation are performed.

A simulation investigation on interaction mechanism between Ebola nucleoprotein and VP35 peptide.

Ebola viruses (EBOV) will induce acute hemorrhagic fever, which is fatal to humans and nonhuman primates. The combination of EBOV VP35 peptide with nucleoprotein N-terminal (NPNTD) is proposed based on static crystal structures in recent studies, but VP35 binding mechanism and conformational dynamics are still unclear. This investigation, using Molecular Dynamic (MD) simulation and Molecular Mechanics Generalized Born Surface Area (MM-GB/SA) energy calculation, more convincingly proves the greater roles of the protein binding mechanisms than do hints from the static crystal structure observations.

Exploration micromechanism of VP35 IID interaction and recognition dsRNA: A molecular dynamics simulation.

Multifunctional viral protein (VP35) encoded by the highly pathogenic Ebola viruses (EBOVs) can antagonize host double-stranded RNA (dsRNA) sensors and immune response because of the simultaneous recognition of dsRNA backbone and blunt ends. Mutation of select hydrophobic conserved basic residues within the VP35 inhibitory domain (IID) abrogates its dsRNA-binding activity, and impairs VP35-mediated interferon (IFN) antagonism. Herein the detailed binding mechanism between dsRNA and WT, single mutant, and double mutant were investigated by all-atom molecular dynamics (MD) simulation and binding energy calculation.

Molecular dynamics exploration of the binding mechanism and properties of single-walled carbon nanotube to WT and mutant VP35 FBP region of Ebola virus.

VP35 of Ebola viruses (EBOVs) is an attractive potential target because of its multifunction. All-atom molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born surface area (MM/GBSA) energy calculations are performed to investigate the single-walled carbon nanotube (SWCNT) as an inhibitor in wild-type (WT) VP35 as well as in three primary mutants (K248A, I295A, and K248A/I295A) through docking the SWCNT in the first basic patch (FBP) of VP35. The SWCNTs of all the four systems effectively bind to the FBP.

Insights into resistance mechanism of the macrolide biosensor protein MphR(A) binding to macrolide antibiotic erythromycin by molecular dynamics simulation.

Macrolide biosensor protein MphR(A) has been known as a key regulatory protein in metabolite sensing and genetic expression regulating. MphR(A) protein binds to macrolide antibiotic erythromycin (Ery) and releases the gene operon, thus activates expression of the mphA gene and initiates Ery resistance. The two mutant amino acid residues (V66L and V126L) might potentially disrupt Ery binding to MphR(A).

Exploring interaction mechanisms of the inhibitor binding to the VP35 IID region of Ebola virus by all atom molecular dynamics simulation method.

Ebola viruses (EBOVs) cause an acute and serious illness which is often fatal if untreated, and there is no effective vaccine until now. Multifunctional VP35 is critical for viral replication, RNA silencing suppression and nucleocapsid formation, and it is considered as a future target for the molecular biology technique. In the present work, the binding of inhibitor pyrrole-based compounds (GA017) to wild-type (WT), single (K248A, K251A, and I295A), and double (K248A/I295A) mutant VP35 were investigated by all-atom molecular dynamic (MD) simulations and Molecular Mechanics Generalized Born surface area (MM/GBSA) energy calculation.