Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico

Perspective

Angiotensin Converting Enzyme (ACE) regulates blood pressure and electrolyte balance by
converting angiotensin I into angiotensin II, which acts as vasoconstrictor and aldosterone-
stimulating peptide. ACE is also known to inactivate vasodilators, bradykinin and angiotensin
17 peptide. Thus, the down-regulation of ACE activity would be very beneficial in various
cardiovascular diseases. In present in silico approach, virtual screening was performed to
identify possible novel inhibitors of testis ACE (tACE) from ZINC database using
Dockblaster. All screened compounds were filtered through Lipinskis rules and other
properties. PyRx tool was then implemented to dock selected compounds. Finally, ligand
ZINC48251687 re-docked using Autodock 4.2 with His 383, His 387 and Glu 411 as flexible
residues of tACE. Molecular Dynamics simulation was then carried out to investigate the
binding stability of the screened ligand in a dynamic environment. It has been observed that
tACE-ligand complex was quite stable over the entire simulation run. We found that ligand
was stabilized by strong hydrogen bonding interactions with Ala 354, Ala 356, Tyr 523 and
Zn2+ of tACE. Thus, ZINC48251687 could be used as starting point for the development of
new non-peptidic inhibitor of tACE and for designing drug against cardiovascular and related
renal diseases.

Keywords

Angiotensin converting enzymeACE inhibitorsADME/toxMolecular dockingMolecular

dynamics simulationVirtual screening