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Simulating virus-host interaction

Researchers assess how viral fusion protein promotes membrane fusion

Oeiras 23.04.2015

The influenza virus is covered by a lipid membrane, which must fuse with the membrane of the host cell for infection to occur. This process is mediated by a viral fusion protein called hemagglutinin. Researchers from the Protein Modelling Lab used computer simulations to understand how this protein, or part of it, promotes membrane fusion. The work is published in the Journal of Chemical Information and Modeling.

Influenza or common flu, caused by the influenza virus, is usually a mild infection but complications may arise, and the virus is known to cause hundreds of thousands of deaths every year. A promising strategy to fight the influenza virus consists in inactivating fusion between the viral and host membranes and the fusion protein is thus an attractive study object. In their work, researchers focused on one extremity of the fusion protein (the N-terminal), which inserts into the host membrane during the fusion process and promotes lipid mixing. Many studies have focused on this protein region, called the fusion peptide, but its mechanism of action is not clear.

Through molecular dynamics simulations, researchers analysed the structure of the isolated fusion peptide in the presence of a membrane. Initial simulations, placing the peptide outside the membrane, were not conclusive. Researchers then built a system where the simulation box has all the components – peptide, lipids, and water – but is left to spontaneously assemble, given the components’ physical properties. Using this strategy, researchers found that the fusion peptide can adopt a membrane-spanning conformation, something that had never been observed before. In these circumstances, the fusion peptide disorders the lipids around it, promoting the intrusion of lipid polar heads and the protrusion of lipid tails, thus destabilizing the membrane.

Researchers believe these findings may help developing new drugs against the influenza virus. “Protein modeling is increasingly applied to the drug discovery process” explains Bruno Victor, first author of this study and ITQB alumnus, who now integrates the team of BSIM2, a spin-off company dedicated to computer driven drug discovery for neurodegenerative amyloid diseases. “Some molecular processes are not amenable to experimental methods and computational biology cannot only shed light on those processes but also narrow the number molecules which need to be experimentally assessed when designing new drugs”, he adds.

Original Article

J. Chem. Inf. Model. (2015) DOI: 10.1021/ci500756v

Self-Assembly Molecular Dynamics Simulations Shed Light into the Interaction of the Influenza Fusion Peptide with a Membrane Bilayer

Bruno L. Victor , Diana Lousa , Jorge M. Antunes , and Cláudio M. Soares


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