Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Poster Abstracts

9-POS Board 9 IN SILICO ENGINEERING AND MEMBRANE-AWARE REFINEMENT OF CHIMERIC HBV-S/PRES1 PROTEINS FOR ENHANCED EPITOPE EXPOSURE Cezar-Gabriel Popescu 1 ; Mihaela Olivia Dobrica 2 ; Teodor Asvadur Sulea 1 ; Norica Nichita 2 ; Laurentiu Spiridon 1 ; Andrei-José Petrescu 1 ; 1 Institute of Biochemistry of the Romanian Academy, Dept. of Bioinformatics & Structural Biochemistry, Bucharest, Romania 2 Institute of Biochemistry of the Romanian Academy, Dept. of Viral Glycoproteins, Bucharest, Romania An effective strategy for the development of effective subunit vaccines involves the insertion of immunogenic epitopes into scaffold proteins without compromising their overall structural integrity. In this study, we employed a structural bioinformatics pipeline to engineer the Hepatitis B Virus (HBV) S membrane protein by inserting two HBV-L preS1 epitopes at five distinct sites. While one site was previously identified in literature, four novel sites were selected based on antigenic potential, membrane proximity, and the conservation of endogenous disulfide bridges. Given the significant length of presS1 inserts the five models were tested for structural stability solvent and exposure maximisation. To this end a multi-stage equilibration workflow was used to stabilize the chimeras followed by Molecular Dynamics. Results were used to investigate the epitope location with respect to the chimera membrane embeding, to assess the thermal stability of the model structure and rank preS1-HBV-S chimeras for the most structurally viable insertion sites that maximize solvent exposure of the preS1 peptide while maintaining the overall scaffold stability. The optimized candidates are proposed for subsequent in vivo immunogenicity testing, providing a robust computational framework for membrane-associated antigen design.

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