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), an integral membrane protein that catalyzes the cleavage of angiotensin I decapeptide to angiotensin II octapeptide. By inhibiting ACE, HSA plays a key role in the renin-angiotensin-aldosterone system (RAAS). However, little is known about the mechanism of interaction between these proteins; the structure of the HSA–ACE complex has not yet been obtained experimentally. The purpose of the present work is to investigate the interaction of HSA with ACE in silico. Ten possible HSA–ACE complexes were obtained by the procedure of macromolecular docking. Based on the number of steric and polar contacts between the proteins, the leading complex was selected, the stability of which was then tested by molecular dynamics (MD) simulation. An analysis of the possible effect of modifications in the albumin molecule on its interaction with ACE was performed. A comparative analysis of the structure of the HSA–ACE complex obtained by us, was performed with the known crystal structure of the HSA complex with neonatal Fc receptor (FcRn). The molecular modeling data outline the direction for further study of the mechanisms of HSA–ACE interaction in vitro. Information about these mechanisms will help in the design and improvement of pharmacotherapy aimed at modulating the physiological activity of ACE.