Exploring the Dynamics of Dengue Virus Envelope Protein by Temperature and pH Variations

Environmental factors such as temperature and pH profoundly influence viral protein
behavior, yet their specific effects on the dynamics of the Dengue virus envelope (E)
protein remain insufficiently characterized. In this study, we investigated how
variations in temperature and pH modulate the conformational flexibility of the E
protein from Dengue virus serotypes 2 and 3 (DENV-2/3), a critical determinant of
viral entry and membrane fusion. Using essential dynamics analysis from extensive
molecular dynamics simulations, we evaluated the structural responses of the E
protein under a range of conditions: pH 5, 6, and 7, and temperatures of 28 °C,
37 °C, and 40 °C. Our findings show that acidic pH and lower temperatures
significantly alter inter-domain motions and global protein flexibility, promoting
conformational transitions that may facilitate fusion in the endosomal environment.
Moreover, the differences observed between mosquito-like (28 °C) and human-like
(37 °C) temperatures suggest an adaptive mechanism enabling the virus to function
efficiently in both hosts. These results highlight the E protein’s sensitivity to
environmental factors and provide new insights into how such modulation may
influence viral infectivity, host specificity, and immune evasion. Overall, this work
emphasizes the importance of modeling physiologically relevant conditions to better
understand the molecular mechanisms underlying DENV pathogenesis.