New pockets in dengue virus 2 surface identified by molecular dynamics simulation.

Area of Science:

• Structural biology
• Computational chemistry
• Virology

Background:

• Limited structural information of disease-related proteins hinders drug discovery.
• Computational chemistry tools can identify novel cavities in protein structures for lead compound identification.
• The dengue virus E protein's conformational changes are critical for the pH-dependent fusion process.

Purpose of the Study:

• To identify new pockets in the dengue virus E protein.
• To evaluate the influence of acidic pH on these pockets.
• To find potential targets for dengue disease inhibitors.

Main Methods:

• All-atom molecular dynamics simulations with explicit solvent.
• Modeling of physiological neutral and acidic endosomal pH conditions.
• Analysis of ectodomain portions of the dengue virus E protein.

Main Results:

• Several pockets with pH-dependent characteristics were identified at chain contact regions.
• Pockets at protein-protein interfaces, induced by monomer-monomer interactions, were discovered.
• Identified pockets show potential for designing lead compounds targeting viral fusion.

Conclusions:

• The study identified novel, pH-sensitive pockets in the dengue virus E protein.
• These pockets represent promising targets for developing inhibitors of viral entry and dengue disease.
• Computational approaches are valuable for discovering new therapeutic strategies against viral infections.