Discovery of small molecules as HPV16 E6 protein inhibitors against cervical cancer: An in silico and biophysical approach

All the input files used for molecular docking and molecular dynamics simulations performed with HPV16 E6 protein to find potential inhibitors.

Considering the critical role of high-risk HPV E6 protein in malignant tumorigenesis, it is widely recognized as a therapeutic target to develop novel and effective treatments for CC. In this work, we explored computational methods to discover new E6 inhibitors with potential interest in CC therapy. Using the E6 protein structure published in the Protein Data Bank (4XR8), molecular docking studies and molecular dynamics simulations were performed to predict the binding energy and orientation of synthetic compounds at the E6-p53 binding site. For experimental studies, the recombinant MBP-E6 protein was expressed from the Escherichia coli host, and affinity chromatography was applied to obtain highly pure protein. Circular dichroism confirmed that the target protein adopts an α-helical, random coil, and β-sheet structure. Finally, a thermal shift assay was used to access potential protein-ligand interactions.