All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

Abstract

Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10(6) all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200,000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

Complete virus capsid at all-atom resolution: Simulations using molecular dynamics and hybrid molecular dynamics/hydrodynamics methods reveal semipermeable membrane function

“…This is in contrast to water molecules that possess the ability of transiting across the capsid wall in both directions. All-atom MD simulation of poliovirus in [9] exhibits similar behaviour of molecular permeability of the poliovirus capsid. The authors concluded that the poliovirus capsid can work as semipermeable membrane.…”

“…We show that water exhibits substantial rate of exchange across the capsid's wall, while ions essentially do not permeate the wall. This make the capsid shell to function as a semipermeable membrane, the behaviour also demonstrated for other viruses [9].…”

Hepatitis B Virus Capsids Have Diverse Structural Responses to Small-Molecule Ligands Bound to the Heteroaryldihydropyrimidine Pocket

“…We therefore suggest a dynamic as well as a structural basis for HAP antiviral activity. A dynamic capsid is not unique to HBV, as demonstrated in studies with picornaviruses (49,65) and HIV (66). We therefore propose that small molecules that limit dynamic ensembles can serve as an effective approach to antiviral treatment.…”

Effects of RNA branching on the electrostatic stabilization of viruses

“…There have been several theoretical studies that investigate the osmotic pressure of ssRNA viruses [28,31,[35][36][37]. Siber and Podgornik showed that the filled ssRNA virions exhibit a small residual negative osmotic pressure, which depends strongly on the amount of capsid charges and can be turned positive with relatively higher capsid charge [28].…”