title: Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations.
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.
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China.
authors.forename: Ronghong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Bai
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Connors
authors.affiliation: Protein Expression Facility, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Linda H L
authors.initials: LH
authors.lastname: Lua
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Yap P
authors.initials: YP
authors.lastname: Chuan
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Anton P J
authors.initials: AP
authors.lastname: Middelberg
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D002152:Calorimetry, Differential Scanning; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D056004:Molecular Dynamics Simulation; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D036022:Capsid Proteins; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle