Thermodynamic variations at the HPV E1-E2 interface correlate with clinical risk groups: an in-silico analysis

Area of Science:

• Virology
• Structural Biology
• Computational Biology

Background:

• Human Papillomavirus (HPV) is a major cause of cancers, particularly cervical cancer.
• The HPV E1 protein is essential for viral genome replication and oncogenesis.
• E1's conserved enzymatic core makes it a target for antiviral therapies.

Purpose of the Study:

• To investigate the structural and functional roles of the HPV E1 protein using in silico methods.
• To identify conserved regions and analyze the E1-E2 protein interaction.
• To explore the thermodynamic differences between E1-E2 complexes of varying oncogenic risk.

Main Methods:

• In silico analysis of HPV E1 sequences and structural modeling with AlphaFold3.
• Multiple sequence alignment to identify conserved residues and evolutionary relationships.
• Thermodynamic profiling to predict binding energies and evaluate E1-E2 complex stability.

Main Results:

• The C-terminal helicase domain of E1 is highly conserved, particularly catalytic motifs.
• Conserved residues in E1 cluster near DNA-binding and E2 interaction surfaces.
• E1-E2 complexes from low-risk HPV types showed higher predicted stability than high-risk types (p < 0.001).

Conclusions:

• The conserved E1 enzymatic machinery is vital for HPV replication.
• Thermodynamic differences at the E1-E2 interface distinguish HPV pathogenicity.
• In silico findings provide a basis for understanding E1-E2 function and motivate experimental validation.