Predicted Configuration and Stability of the ATAD2/SOX10 Complex Using Molecular Dynamics Simulations.

Abstract

ATAD2, a melanoma competence factor, forms a protein complex with SOX10 that facilitates expression of SOX10 developmental target genes. The complex enables a strong transcriptional response to oncogenes such as BRAFV600E and is sufficient to endow oncogenic competence to melanocytes. The elucidation of the ADAT2/SOX10 complex structure may facilitate the development of drugs that can block formation of the complex. We used the ClusPro web server for protein-protein docking to visualize and analyze the complex and GROMACS to perform molecular dynamics simulations. ClusPro protein docking analysis demonstrated the central position of ADAT2 in the ADAT2/SOX10 complex. Molecular dynamics simulations of ATAD2 docked to SOX10 suggest that ATAD2/SOX10 is not a stable structure. The central position of ADAT2 in the complex suggested that ADAT2 complexed to SOX10 may have the capability to modify multiple functions of the latter, one of which allows BRAFV600E to impart increased oncogenic function to melanocytes. The results of the molecular dynamics simulations imply that the ADAT2/SOX10 complex is not stable and might be disrupted by a therapeutic molecule, reducing the risk of melanoma. Knowledge of the ADAT2/SOX10 complex structure may facilitate the development of drugs that can block complex formation.