Computational Perspectives on the Assembly Mechanism of PBCV-1: A Review Integrating Structural and Experimental Evidence

Giant double-stranded DNA (dsDNA) viruses such as Paramecium bursaria chlorella virus 1 (PBCV-1) exhibit complex assembly pathways shaped by global protein symmetry, local asymmetry and an internal membrane scaffold. Cryo-electron microscopy has resolved the [Formula: see text]169 d lattice and unique vertex architecture of the PBCV-1 capsid, while structural and lipidomic studies highlight the contribution of the internal membrane to infection and virion stability. Yet, the dynamic processes through which thousands of Vp54 trimers and membrane components coalesce into a complete virion remain poorly understood. Computational methods, including electrostatics, molecular dynamics, coarse-grained modeling and multiscale simulations, have emerged as powerful tools to complement experimental findings and elucidate the physicochemical rules of assembly. In this review, we synthesize current structural and functional knowledge of PBCV-1, emphasize emerging computational advances and integrate cross-system examples to outline transferable principles. Together, these perspectives chart a roadmap toward predictive modeling of giant virus assembly and the coupling between membranes and capsids.