Scope of Theoretical Approaches Studying the Ligand-Nrf2 Interactions

Abstract

The nuclear factor erythroid 2-related factor 2 (Nrf2) is a protein transcriptional factor considered as an emerging target for multiple biological processes. Its study could be useful to develop new treatments. Theoretical approaches have led to investigating the relevance of nuanced details in the structure of that protein. Also, after the X-ray crystals reporting Nrf2-KEAP1 interactions and identification of sites for potential interaction of other proteins and small compounds, the number of reports regarding these interactions is increasing. In this chapter, the advancements of theoretical approaches were collected and presented as useful to apply for developing therapeutic tools. First, information regarding the structure of Nrf2, as well as the observed interactions in crystal complexes is presented and commented. Thereafter, the identified sites of interest for letting interactions of natural compounds or small drugs which are proposed as potential drugs are presented. Finally, the advances and limitations of the theoretical assays, as well as the relationship with data reported experimental assays and the potential applications in medicine, are stated. Updated advancements by application of theoretical approach for understanding ligand interactions on Nrf2 are helpful to understand the biological activity of Nrf2 and the origin of some fails involved in etiology and pathophysiology of some human diseases.