Virus Disassembly Pathways Predicted from Geometry and Configuration Energy
Virus are supramolecular structures that are responsible for some of the most significant epidemics around the world. The disassembly of virus particles, a key event during viral infection is triggered by numerous intracellular factors. The investigation of the mechanisms of protein subunit loss during viral disassembly has generally been overlooked, in sharp contrast with the research on the assembly process of virus particles, which has been the focus of both experimental and theoretical studies. In this work, we address the problem of predicting the sequence of protein subunit removal from a viral capsid, by assuming that the order of subunit loss is mainly determined by each capsid’s structural geometry and configuration energy. We modelled the early stages of virus disassembly in a sample of 51 icosahedral viruses of class T = 1, predicting the sequence of removal of up to five subunits. Due to the high symmetry of viral structures, we established the geometrical equivalence of subunit configurations of capsid fragments, decreasing the size of the search space. The energy of a given configuration was estimated by using heuristic functions of the number and types of inter-subunit contacts. We found a disassembly pathway common to a large group of viruses, consisting of the removal of a triangular trimer. Exceptions to this general pattern include the loss of a pentagon-shaped pentamer. These results point at specific subunit interactions as putative targets for novel antiviral drugs developed to interfere with the disassembly process.
KeywordsVirus capsid disassembly Combinatorial geometry Symmetry groups Structural biology
Work supported by project RECI/BBB-BEP/0104/2012 from Fundação para a Ciência e Tecnologia, Portugal. We also had support from the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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