Human papillomavirus 16 (HPV 16) is a DNA virus that is capable of infecting humans and causing cervical cancer. HPV16 E2 plays an important role in viral gene regulation. This work aims to predict the binding conformations and interactions between the dodecapeptides and HPV16 E2 as well as to design novel peptide inhibitors that are capable of binding to HPV16 E2 and disrupt the transcriptional regulator E1-E2 complex formation, using computational protein design techniques. Based on previously reported peptide4 (TWFWPYPYPHLP), novel peptide inhibitors were designed and five peptides that showed lower binding energy to HPV16 E2 than that of peptide4, were selected for in vitro experiments. Enzyme-linked immunosorbent (ELISA) assay showed that Y6R, W4H_Y6R, and W4H peptides bound to HPV16 E2 with higher affinity than peptide4 did. Moreover, Y6R, W4H_Y6R, and W4H peptides more effectively inhibited E1-E2 complex formation than peptide4. This work revealed important interactions between the peptides and E1-E2 complex, suggesting a strategy for development of more potent peptide inhibitors.
Keywords: ClusPro; E1; E2; HPV16; I-TASSER; docking; small peptide inhibitor.
© 2016 John Wiley & Sons A/S.