Coarse-Grained Molecular Dynamics Simulations of the Entire Influenza Virus Envelope

Abstract

The envelope of the influenza virus contains three membrane proteins: hemagglutinin (HA), neuraminidase (NA) and the M2 proton channel. The interactions of these proteins with their surrounding lipid environment are important for many phases of the viral life cycle. In the various membranes of an infected host cell, newly formed viral proteins are thought to use lipid rafts - small patches of ordered membrane - to locate themselves at the plasma membrane. The arrangement of the proteins within the envelope of free virions may also be important for the infectivity of the virus.We have used the MARTINI coarse-grained force field to simulate a viral envelope of realistic size for several microseconds. Coarse-grained methods allow simulations on large systems (4.5 million particles for the system in this work) over extended timescales. Using information from recent cryo-electron tomography images of complete virions as a basis, our model has been constructed as a 60 nm diameter lipid vesicle with 80 HA, 12 NA and 12 M2 proteins inserted in the membrane. The protein structures are derived from existing crystallographic and NMR structures. The vesicle membrane is a ternary mixture of saturated and poly-unsaturated phospholipids, and cholesterol, which has been shown in other work to separate into raft and non-raft phases.The simulations will be analysed to provide information on the structural and dynamical properties of the viral envelope. In particular, we will focus on the partitioning of proteins between raft and non-raft lipid domains, and the degree of protein clustering.