E7 oncoprotein of human papillomavirus: Structural dynamics and inhibitor screening study

Area of Science:

• Structural biology
• Virology
• Computational chemistry

Background:

• Human papillomavirus (HPV) is the primary cause of cervical cancer.
• The HPV E7 oncoprotein plays a crucial role in cellular transformation and cancer development.
• Understanding E7's structure and function is vital for developing anti-HPV agents.

Purpose of the Study:

• To investigate the evolutionary relationships of HPV E7.
• To generate a 3D homology model of HPV 16 E7.
• To identify potential therapeutic compounds targeting HPV E7.

Main Methods:

• 3D homology modeling of HPV 16 E7.
• Molecular dynamics simulations (100 ns) for stability and flexibility analysis.
• Molecular Recognition Features (MoRFs) analysis to identify disordered binding sites.
• Virtual screening and molecular dynamics simulations for lead compound identification and validation.

Main Results:

• A validated 3D homology model of full-length HPV 16 E7 was generated.
• Disordered-based binding sites on E7 were identified using MoRFs analysis.
• Potential lead compounds targeting the structured C-terminal region of E7 were identified and validated.

Conclusions:

• This study provides insights into the structural and functional aspects of HPV E7, including its disordered regions.
• Identified lead compounds show potential as therapeutic agents against HPV.
• The findings contribute to the development of novel anti-HPV drugs targeting E7 oncoprotein.