Interaction of Albumin with Angiotensin-I-Converting Enzyme According to Molecular Modeling Data

Human serum albumin (HSA) is an endogenous inhibitor of angiotensin-I-converting enzyme (ACE), which is an integral membrane protein catalyzing the cleavage of decapeptide angiotensin I to octapeptide angiotensin II. By inhibiting ACE, HSA plays an important role in the renin-angiotensin-aldosterone system (RAAS). However, little is known about the mechanism of interaction between these proteins, and the structure of the HSA–ACE complex has not yet been experimentally obtained. The aim of the presented work is to investigate the interaction of HSA with ACE by molecular modeling methods. Ten possible HSA–ACE complexes were obtained by macromolecular docking method. The leader complex was selected according to the number of steric and polar contacts between the proteins, and its stability was tested by molecular dynamics (MD) simulation. The possible effect of modifications in the albumin molecule on its interaction with ACE was analyzed. A comparative analysis of the structure of the obtained HSA–ACE complex with the known crystal structure of the HSA complex with neonatal Fc receptor (FcRn) was performed. The obtained results of molecular modeling define a direction for further in vitro studies of the mechanisms of HSA–ACE interaction. Information about these mechanisms will help in the design and improvement of pharmacotherapy aimed at modulating the physiological activity of ACE.