Abstract
Flock House virus (FHV) is a well-characterized model system to study infection mechanisms in non-enveloped viruses. A key stage of the infection cycle is the disruption of the endosomal membrane by a component of the FHV capsid, the membrane active γ peptide. In this study, we perform all-atom molecular dynamics simulations of the 21 N-terminal residues of the γ peptide interacting with membranes of differing compositions. We carry out umbrella sampling calculations to study the folding of the peptide to a helical state in homogenous and heterogeneous membranes consisting of neutral and anionic lipids. From the trajectory data, we evaluate folding energetics and dissect the mechanism of folding in the different membrane environments. We conclude the study by analyzing the extent of configurational sampling by performing time-lagged independent component analysis.
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Acknowledgements
This work has been supported by the National Institutes of Health through grant R35GM119762 to E.R.M. Computational resources have been provided through the University of Connecticut Hornet HPC cluster and NSF XSEDE program (grant number TG-MCB140016). We thank Kevin Boyd for his critical reading and providing constructive suggestions on this manuscript.
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This study was funded by NIH (grant number R35GM119762).
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Nangia, S., Pattis, J.G. & May, E.R. Folding a viral peptide in different membrane environments: pathway and sampling analyses. J Biol Phys 44, 195–209 (2018). https://doi.org/10.1007/s10867-018-9490-y
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DOI: https://doi.org/10.1007/s10867-018-9490-y