Flaviviruses are enveloped, positive-sense RNA viruses that include dengue (DENV), West Nile, Zika, tick-borne encephalitis, and yellow fever viruses. Among them, DENV represents a major global health burden, causing hundreds of millions of infections annually. The virus exists as four antigenically distinct serotypes, which complicates vaccine development because cross-reactive antibodies can contribute to antibody-dependent enhancement. Although a dengue vaccine has been licensed, its protective efficacy is limited and safety concerns remain, highlighting the need for improved immunogen design strategies.The DENV virion is approximately 50 nm in diameter and consists of a lipid envelope containing 90 envelope and membrane protein dimers that surround the capsid and viral RNA genome. Throughout its life cycle, the virus undergoes substantial structural rearrangements driven by environmental factors such as pH, temperature, and maturation state. These transitions alter the organization of the viral surface and modulate the exposure and accessibility of key immunogenic epitopes, presenting a significant challenge for vaccine design.In this work, we applied multiscale molecular dynamics simulations, integrated with available experimental structural data, to investigate the conformational dynamics of DENV particles. We analyzed epitope accessibility and structural stability in mature and immature virions as well as in isolated E protein constructs relevant to virus-like particle (VLP) and mRNA vaccine platforms. Simulations were performed across multiple DENV strains and virion morphologies to capture structural variability. Guided by these insights, we also explored rationally designed mutations in the E protein aimed at improving structural stability through optimized protein–protein and protein–lipid interactions. Together, our results provide mechanistic insight into the dynamic presentation of dengue epitopes and establish a structural framework to support the rational design of next-generation dengue immunogens with improved stability, safety, and immunogenicity.