Integrative structural biology of HIV-1 capsid protein assemblies: combining experiment and computation

HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS), a global pandemic that has claimed 32.7 million lives since 1981. Despite decades of research, there is no cure for the disease, with 38 million people currently infected with HIV. Attractive therapeutic targets for drug development are mature HIV-1 capsids, immature Gag polyprotein assemblies, and Gag maturation intermediates, although their complex architectures, pleomorphism, and dynamics render these assemblies challenging for structural biology. The recent development of integrative approaches, combining experimental and computational methods has enabled atomic-level characterization of structures and dynamics of capsid and Gag assemblies, and revealed their interactions with small-molecule inhibitors and host factors. These structures provide important insights that will guide the development of capsid and maturation inhibitors.