Transcriptional regulation depends on sequence-specific binding of regulatory proteins to their responsive elements in viral DNA. The papillomavirus E2 protein binds to DNA through the consensus sequence ACCG-NNNN-CGGT, activating or inhibiting viral replication. Through molecular dynamics simulations we were able to characterize the role of the DNA molecule on E2 binding region (named α 1 E2) conformation, acquiring structural insights for previous works suggesting an unfolded to folded transition upon α 1 E2 complexation to DNA. Moreover, the results indicate sites to guide the design of α 1 E2 synthetic derivatives to inhibit the HPV infection.