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Identifying Disassembly units in Viral Capsids
Location: 59
Mentor: Dr. Antoni Luque
Background: Viruses protect their infectious genomes in protein shells called capsids, which are assembled from multiple copies of the major capsid protein and sometimes minor proteins. Viral capsids often include maturation steps that stabilize the capsid. The study of capsid disassembly is of great interest as a potential antiviral strategy, but disassembly experiments are challenging and the molecular steps that initiate disassembly are often uncertain.
Aim: The goal of this research is to establish a reliable approach to predict the regions of viral capsids that are more prone to disassemble.
Methods: The structural bioinformatics tool pyCapsid was applied to investigate the capsids of seven viruses, which had been previously characterized to disassemble experimentally. The main steps of the bioinformatics method included loading the PDB file, coarse graining the amino acids as point masses around their alpha-carbon (nodes) and establishing springs between these nodes to account for the interactions between the amino-acids near equilibrium (elastic network model). The normal modes of the hessian matrix were obtained and calibrated to reproduce the fluctuations (B-factors) of the amino-acids. A quasi-rigid clustering criteria was applied to identify the mechanical units in the capsid. These quasi-rigid regions were interpreted as the regions more likely to initiate the disassembly process.
Results: The predicted disassembly units in the different viruses included dimers all the way to mega-pentamers, depending on the capsid. The predictions for the seven viruses were consistent with the disassembly units observed experimentally.
Conclusion: The quasi-rigid domain approach generated by pyCapsid provided a reliable method to identify the disassembly units of viral capsids.
