Investigation of a predicted N-terminal amphipathic α-helix using atomistic molecular dynamics simulation of a complete prototype poliovirus virion

The wild type 1 poliovirus capsid was first described in atomic detail in 1985 using X-ray crystallography. Numerous poliovirus capsid structures have been produced since, but none resolved the spatial positioning and conformation of a predicted N-terminal α-helix of the capsid protein VP1, which is considered critical to virus replication. We studied the helical structure under varying conditions using in silico reconstruction and atomistic molecular dynamics (MD) simulation methods based on the available poliovirus capsid atom coordinate data. MD simulations were performed on the detached N-terminal VP1 helix, the biologically active pentamer form of the pre-virion structure, reconstructed empty virus capsids and a full virion containing the poliovirus RNA genome in the form of a supercoiled structure. The N-terminal α-helix structure proved to be stable and amphipathic under all conditions studied. We propose that a combination of spatial disorder and proximity to the genomic RNA made this particular structure difficult to resolve by X-ray crystallography. Given the similarity of our in silico model of poliovirus compared to X-ray crystallography data, we consider computational methods to be a useful complement to the study of picornaviruses and other viruses that exhibit icosahedral symmetry.

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► We constructed an atomistic model of a complete prototype wild poliovirus.
► Using available data we reconstructed missing protein and RNA structures.
► We performed atomistic MD simulations up to 4 million atoms in size for 10 ns.
► We investigated the stability of a predicted but unresolved N-terminal amphipathic helix.
► The techniques used can be applied to other viruses with icosahedral symmetry.