Elucidating the interactions of advanced glycation end products with RAGE, employing molecular docking and MD simulation approaches: Implications of potent therapeutic for diabetes and its related complications

Abstract

Diabetes mellitus is a global health challenge, ranking third among the mortality rates globally. Diabetic-mediated Advanced glycation end products (AGEs) associated with Receptor for Advanced Glycation End-products (RAGE) contribute to chronic diabetes and its complications, inflammatory, cancer, and neurodegenerative disorders. The information behind the binding mechanisms between AGEs-RAGE complexes remains elusive. In the current study, we used advanced computational approaches to reveal the intramolecular interactions of AGEs-RAGE which leads to multiple diseases. We have characterized AGEs-RAGE interactions by protein–ligand docking and molecular dynamic (MD) simulations were further conducted to evaluate the AGEs-RAGE complex stability. Subsequently, several residues emerged as pivotal in AGEs-RAGE complex formation. Further, MD simulation provides valuable insights into structural movements, stability, and conformational dynamics of protein–ligand complexes. Our findings underscore new insights into molecular mechanisms of AGEs-RAGE complex formation in diabetes and its related complications and the ease of the drug discovery process.