Abstract

Angiotensin-I-Converting Enzyme (ACE) is a critical component of the renin-angiotensin system, playing a vital role in blood pressure regulation and fluid-electrolyte balance. While its primary function is the cleavage of angiotensin I, its interaction with other circulating proteins, such as albumin, remains a subject of interest, particularly in the context of physiological regulation and drug pharmacokinetics. This study utilized advanced molecular modeling techniques, including molecular docking and molecular dynamics simulations, to investigate the structural and energetic basis of the interaction between human serum albumin and ACE. The primary objective was to identify potential binding sites and characterize the stability of the resulting complex. Our findings reveal a novel, high-affinity binding interface on the ACE surface for albumin, distinct from the active site, suggesting an allosteric regulatory mechanism. The molecular dynamics simulations indicate that this interaction is stable and involves key residues that may influence ACE conformation and, consequently, its enzymatic activity or membrane association. These in silico results provide a foundational understanding of a previously uncharacterized protein-protein interaction, offering new insights into the complex regulatory network of the cardiovascular system and potentially guiding the development of more targeted ACE inhibitors or therapeutic strategies for conditions like hypertension and chronic kidney disease.