Full scale simulations of viruses

What is it about?

To become infectious, retroviruses like HIV-1 mature within a bilayer lipid envelope commandeered from the host cell. HIV-1 is known to enrich this viral membrane with sphingomyelins and cholesterol, molecules which alter membrane fluidity and other physical properties, and incorporate more than 20 unique chemical species that are distributed heterogeneously across bilayer leaflets. Intriguingly, the presence of low-mobility raft domains which emerge from this complex composition are thought to play a role in directing the localization of structural proteins that constitute the viral capsid. Moreover, the chemical composition of the leaflets comprising the bilayer are believed to exist in dynamic equilibrium, through transverse exchange of lipids known as lipid flip-flop, which might relate to curvature and regulate the binding of lipids to HIV-1 proteins during maturation. There exist as-yet understood roles for the viral liposome’s asymmetric, cholesterol-rich composition that must be fulfilled for HIV-1 to reach a mature and infectious state. Employing the power of massively parallel supercomputers, scientists at the University of Delaware construct and simulate a full scale model of the HIV liposome, featuring 24 distinct lipid species and an authentic, asymmetric composition. Using cutting edge analyses, the authors show that the membrane remains fluid, but is marked by the presence low-mobility raft regions. Further, they show that lipid flip-flop occurs spontaneously in the vesicular system, but not when the bilayer is arranged in a flat configuration. Altogether, their results show that a variety of complex behavior is made possible by HIV’s unique lipid profile.

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Why is it important?

Viral membranes are essential for retroviral infection, and understanding their chemical and physical behavior is an important step toward characterizing the complete viral particle. Observing single-lipid level phenomena, such as coordination within raft domains and transverse diffusion across leaflets, remains challenging using experimental techniques alone. In concert with experimental data, the authors show how high performance computing can be leveraged to study immense and highly complex lipid systems, and further show that such complexity and scale are required for the emergence of mesoscopic phenomena.