Spatially ordered systems confined to surfaces such as spheres exhibit interesting topological structures because of curvature induced frustration in orientational and translational order.
High mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects but variants carrying them are rapidly purged. Surprisingly, a particular variant incapable of entering host cells is rescued by host antibodies targeting HIV-1. Understanding the molecular mechanism of this rescue would be important to develop and improve antibody-based therapies. We performed fully atomistic molecular dynamics simulations of the HIV-1 gp41 trimer responsible for viral entry into host cells, its entry-deficient variant, and its complex with the rescuing antibody, to unravel the underlying mechanisms. We find that the Q563R mutation, which the entry-deficient variant carries, prevents the native conformation of the gp41 6-helix bundle required for entry and stabilizes an alternative conformation instead. This is the consequence of substantial changes in the secondary structure and interactions between the domains of gp41. Binding of the antibody F240 to gp41 reverses these changes and re-establishes the native conformation, resulting in rescue. To test the generality of this mechanism, we performed simulations with the entry-deficient L565A variant and antibody 3D6. We find again that 3D6 binding was able to reverse structural and interaction changes introduced by the mutation and restore the native gp41 conformation. Viral variants may not only escape antibodies but be aided by them in their survival, potentially compromising antibody-based therapies including vaccination and passive immunization. Our simulation framework could serve as a tool to assess the likelihood of such resistance arising against specific antibodies.
Spatially ordered systems confined to surfaces such as spheres exhibit interesting topological structures because of curvature induced frustration in orientational as well as translational order. The study of these structures is important for investigating the interplay between geometry, topology, and elasticity, and for their potential applications in materials science. In this work we numerically simulate a spherical monolayer of soft repulsive spherocylinders (SRS) and study the packing of rods and their ordering transition as a function of the packing fraction. In the model that we study, centers of mass of the spherocylinders (situated at their geometric centers) are constrained to move on a spherical surface. The spherocylinders are free to rotate about any axis that passes through their respective centers of mass. We show that at relatively lower packing fractions, there is a continuous transition from a disordered fluid to a novel, orientationally ordered, spherical fluid monolayer as the packing fractions is increased. This monolayer of orientationally ordered SRS particles resembles a hedgehog -long axes of the SRS particles are aligned along the local normal to the sphere. At higher packing fractions, system undergoes transition to the solid phase, which is riddled with topological point defects (disclinations) and grain boundaries that divide the whole surface into several domains.
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