NFAT5, an activated T‐cell factor, plays a regulatory role in a variety of autoimmune processes through specific recognition with DNA. However, the details of the interaction of NFAT5 with DNA are unclear. Focused on the complexes of wild type (WT) and mutant NFAT5 with DNA complexes, respectively, we have conducted research on the conformational and dynamics effects caused by residue mutations through molecular dynamics (MD) simulations combined with MM‐PBSA prediction. According to the results of MM‐PBSA, non‐polar interactions are the main driving force in the interaction between NFAT5 and DNA. At the same time, 26 residues play a key role in the interaction with DNA. The energy decomposition results suggest that extensive interactions between the nitrogenous bases of DNA and NFAT5 are responsible for the specific recognition of DNA by NFAT5. By superimposing the structures of mutants and WT complexes, it was found that mutations not only affect the mutated residues, but also change the binding contribution of other amino acids, hydrogen bonding interactions and the stability of the complexes. These results provide a strong rationale and new ideas for NFAT5 as a new target for the treatment of autoimmune diseases.
The frequent outbreaks of the AIDS (Acquired Immune Deficiency Syndrome) pandemic and the limited availability of anti‐Human Immunodeficiency Virus (HIV) drugs highlight the urgent need to develop new antiviral drugs. A detailed understanding of the interactions between TAR‐Binding Proteins (TBP) and RNA will facilitate the discovery of new anti‐AIDS drugs. In order to characterize and explore the key interactions between RNA and TBP, we focused on the wild type (WT) and three mutant TBPs (TBP6.9, TBP6.7, and TBP6.3) with RNA, multiple molecular dynamics simulation and energy computation were performed. The results showed that 12 key residues played a major role in the interaction between TBP and RNA. The mutated residues of TBP changed the interaction between their surrounding residues and RNA, thus affecting the binding of TBP to RNA. In addition, structural and energy analyses showed that in contrast with WT TBP‐RNA complex, the mutated residues had little effect on the backbone structure of TBP, but changes in the van der Waals interactions and electrostatic interaction associated with the side chains are responsible for the altered the binding between three mutant TBPs and RNA complexes. The discovery of TBP‐RNA recognition mechanism in our work provides some useful insights and new opportunities for the development of anti‐aids drugs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.