In silico studies of the interaction between BRN2 protein and MORE DNA.

The incidence of skin cancer has increased in recent decades, and melanoma is the most aggressive form with the lowest chance of successful treatment. Currently, drug design projects are in progress, but available treatments against metastatic melanoma have not significantly increased survival, and few patients are cured. Thus, new therapeutic agents should be developed as more effective therapeutic options for melanoma. High levels of the BRN2 transcription factor have been related to melanoma development. However, neither the three-dimensional (3D) structure of BRN2 protein nor its POU domain has been determined experimentally. Construction of the BRN2 3D structure, and the study of its interaction with its DNA target, are important strategies for increasing the structural and functional knowledge of this protein. Thus, the aim of this work was to study the interaction between BRN2 and MORE DNA through in silico methods. The full-length BRN2 3D structure was built using the PHYRE2 and Swiss-Model programs, and molecular dynamics of this protein in complex with MORE DNA was simulated for 20 ns by the NAMD program. The BRN2 model obtained includes helix and loop regions, and the BRN2 POU domain shares structural similarity with other members of the transcription factor family. No significant conformational change of this protein occurred during dynamics simulation. These analyses revealed BRN2 residues important for the specific interaction with nucleotide bases and with more than one DNA nucleotide. This study may contribute to the design of inhibitors against BRN2 or MORE DNA as molecular targets of melanoma skin cancer. Graphical Abstract Model of complete Brn2 protein in complex with MORE DNA after building through comparative modeling and refinement by molecular dynamics simulation.