Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective

Abstract

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 1-7 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 Lipinski's 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 Zn 2? 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.

Homology Modeling and Docking Studies of TMPRSS2 with Experimentally Known Inhibitors Camostat Mesylate, Nafamostat and Bromhexine Hydrochloride to Control SARS-Coronavirus-2

“…Homology modelling and molecular docking techniques have been found useful to investigate folding pattern and molecular interactions between several enzymes and ligands [33][34][35][36][37][38][39][40][41][42] AutoDock and UCSF chimera [31].…”

RM1 Semiempirical Model: Chemistry, Pharmaceutical Research, Molecular Biology and Materials Science

“…Indeed, many articles report its use in these contexts. 34,[225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240][241][242][243][244] For example, Aldulaijan and Platts 244 studied the peptide binding to the histocompatibility II receptors. Statistical results indicated a correlation between the half maximal inhibitory concentration (IC 50 ) and RM1-D interaction energy.…”

“…In this sense, RM1 has been widely used as the quantum chemical method to refine molecular docking poses, carry out preliminary conformational searches, calculate atomic partial charges and determine ground state geometries of a set of ligands to further perform molecular docking, high throughput screening calculations or SAR studies. Studies of this kind included: the ability of the tariquidar and elacridar to inhibit the multidrug resistance transporter P-glycoprotein; 231 prediction of the partial atomic charges of the thymidylate kinase obtained from variola virus; 232 drug action mechanisms of a set of chloroquine compounds that present antiplasmodial activity against chloroquine-resistant parasites; 233 glycosidase inhibitors, and immunosuppressive agents that are based on γ-hydroxyethyl piperidine iminosugar and N-alkylated derivatives; 234 the use of gamma radiation to degrade the systems phenylethylamine and tyramine; 235 a ternary complex formation in the catalysis of the Trypanosoma cruzi trans-sialidase, which is an important protein for the therapy of Chagas disease by chemotherapy; 236 geometry optimizations and partial atomic charge quantities of the species involved in the inhibition of nerve agents by oxime BI-6 and acetylcholinesterase; 237 evaluation of the ability of the 1,3,4-thiadiazole and s-triazole derivatives as antimicrobial agents; 238 conformational aspects of the modified nucleosides k 2 C (hypermodified nucleoside lysidine) and t 6 A (hypermodified nucleoside N 6 -(N-threonylcarbonyl) adenosine) that are present in the anticodon loop of the tRNA Ile ; 239 structural properties of the system M. tuberculosis enoyl-acyl carrier protein (ACP) reductase-NADH (protonated nicotinamide dinucleotide), as well as its interaction with the diphenyl ether inhibitors; 240 the identification of the inhibitor of the angiotensin converting enzyme; 242 optimization of the geometries of both a set of 1,4-naphthoquinone derivatives that are capable of inhibiting the P2X7 receptor, which is an ATP-gated ion-channel, 247 as well as of the AMCA-peptide-TAMRA system, where AMCA and TAMRA stand, respectively, for 7-amino-4-methyl-3-coumarinylacetic acid and 5-carboxytetramethylrhodamine; 248 partial atomic charge calculations of oximes, such as HI6 and 2-PAM that are nucleophiles capable of reactivating the inhibited human enzyme acetylcholinesterase; 249 structural calculations of peroxywybutosine present in the 37 th position in the anticodon loop of tRNA Phe when both RM1 and multiple molecular dynamics methods were employed; 250 QM/MM calculations on the mechanism of carboxylation of ribulose-1,5-biphosphate, where RM1 was used in QM part; 251 and geometry optimizations of a set of eight 3-phenylcoumarin derivatives with 6,7-or 5,7-dihydroxyl groups, either free or acetylated, bound to the benzopyrone moiety, in order to study modulation of effect or functions of human neutrophils. 252…”

Evaluation of a Possible Role of <b><i>Stigmatella aurantiaca</i></b> ACE in Aβ Peptide Degradation: A Molecular Modeling Approach

“…Molecular docking and MD simulation are useful techniques and being used successfully to explore mo- Dhanavade and Sonawane, 2014;Jalkute et al, 2015;Parulekar et al, 2013;Tseng et al, 2007]. The predicted model of S. aurantiaca ACE was used as a receptor, whereas Aβ peptide (1AML.pdb) as a ligand molecule.…”