Thermodynamics of binding of angiotensin-converting enzyme inhibitors to enzyme active site model

The density functional theory (DFT) using Becke3LYP functional and the two-layered ONIOM Becke3LYP:MNDO calculations have been carried out to investigate the structural and thermodynamic properties of 29 neutral and deprotonated angiotensin-converting enzyme inhibitors (H2O, enalaprilat, cilazaprilat, imidaprilat, perindoprilat, quinaprilat, ramiprilat, spiraprilat, trandolaprilat, fosinoprilat, omapatrilat, captopril, zofenoprilat, silanediol and keto-ACE) in complex with zinc cation and three first-shell ligands as models of active site of angiotensin-converting enzyme. The influence of deprotonation on the structure and relative energetics of model complexes was examined. Interaction enthalpies and Gibbs energies between inhibitors and angiotensin-converting enzyme active site model were calculated. The structure and thermodynamics of optimized complexes are discussed from the point of view of their biological importance.