Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly

• DOI: 10.1371/journal.pcbi.1006082
• Publication Date: 2018-04-16T17:35:48Z
• Authors: Juan Francisco Viso; Patricia Belelli; Matías Machado; Humberto González; Sergio Pantano; María Julia Amund...; Fernando Zamarreño; Maria Marta Branda; Diego M. A. Guérin; Marcelo D. Costabel
• Keywords: Proton channel; Models, Molecular; QH301-705.5; Static Electricity; Molecular Dynamics Simulation; Molecular Dynamics; QM/MM; Models, Biological; Ion Channels; cytochrome-c-oxidase; models; 03 medical and health sciences; Capsid; https://purl.org/becyt/ford/1.6; Animals; water-molecules; Biology (General); https://purl.org/becyt/ford/1; membrane; particles; 0303 health sciences; Virus Assembly; OH; ion channels; Computational Biology; dynamics; TrV; Hydrogen-Ion Concentration; proteins; 3. Good health; Dicistroviridae; solvation; Protons; Hydrophobic and Hydrophilic Interactions; Research Article

In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in capsid small and non-enveloped icosahedral viruses. With purpose examine Triatoma Virus (TrV) as case study. This virus has stable under highly acidic conditions but disassembles releases genome alkaline environments. Our calculations range from subtle sub-atomic proton interchange to dismantling large-scale system representing several million atoms. results provide structure-based explanations for three roles played by enable release. First, observe, first time, formation hydrophobic gate cavity along five-fold axis wild-type capsid, which can be disrupted an located pore. Second, channel enables protons permeate through unidirectional Grotthuss-like mechanism, is most likely process senses pH. Finally, assuming leak promotes charge imbalance interior model internal pressure forces shell cracking using coarse-grained simulations. Although qualitatively, last step could represent mechanism opening allows RNA All our are agreement with current experimental data obtained TrV describe cascade events explain destabilization disassembly similar