Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/110114
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Type: Journal article
Title: Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations
Author: Zhang, L.
Tang, R.
Bai, S.
Connors, N.
Lua, L.
Chuan, Y.
Middelberg, A.
Sun, Y.
Citation: PLoS ONE, 2014; 9(9):e107313-1-e107313-12
Publisher: Public Library of Science (PLoS)
Issue Date: 2014
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Lin Zhang, Ronghong Tang, Shu Bai, Natalie K. Connors, Linda H.L. Lua, Yap P. Chuan, Anton P.J. Middelberg, Yan Sun
Abstract: The success of recombinant virus-like particles (VLPs) for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV) VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.
Keywords: Antigens; vaccines
Rights: © 2014 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030073505
DOI: 10.1371/journal.pone.0107313
Appears in Collections:Chemical Engineering publications

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