Architecture of SV40 tubular virus nano-particles from an energy landscape perspective: A computational study

Background The polymorphic assembly of polyomaviridae capsids into spherical or tubular nano-particles presents a fundamental challenge in understanding viral self-organization. Objectives Here, we the structural and energetic factors affecting the architecture of non-infectious tubular Simian Virus 40 (SV40) particles, which hold promise for targeted drug delivery. Methodology By uniquely integrating an atomically detailed model of the energy landscape for VP1 pentamer trimers with viral tiling theory, we successfully predicted the structure of these tubular assemblies. Results Our predicted tubular particle diameter (~424 Å) is in close agreement with the experimentally observed range of 400-450 Å, and the predicted arrangement of pentamer subunits on the tubular surface closely mirrors cryo-electron microscopy data. A key finding is that the architecture of these tubular structures is largely determined by the lowest energy inter-pentamer packing within the trimer, observed at pH 5. Furthermore, our model predicts a destabilization of tubular structures at pH 8, consistent with experimental observations and suggesting a pH-dependent assembly mechanism. Conclusion This work provides a crucial mechanistic framework for understanding the physical principles governing capsid polymorphism in polyomaviridae, which can inform the rational design of nano-scale VLPs for nanotechnology and drug delivery.