In-silico characterization of ECE-1 inhibitors

• Published in: Computers in biology and medicine Vol. 42; no. 4; pp. 446 - 457
• Main Authors: Ajay Babu, P, Colluru, Viswa Teja S.S, Anaparthy, Naishitha
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.04.2012; Elsevier Limited
• Subjects: Algorithms; Aspartic Acid Endopeptidases - antagonists & inhibitors; Aspartic Acid Endopeptidases - chemistry; Aspartic Acid Endopeptidases - metabolism; Atherosclerosis; Binding sites; Blood pressure; Cardiovascular disease; Cholesterol; Colleges & universities; Crystal structure; Databases, Protein; Docking; ECE-1; Endothelin; Endothelin converting enzyme; Endothelin-1 - metabolism; Endothelin-Converting Enzymes; Endothelium; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glycopeptides - chemistry; Glycopeptides - metabolism; Graduate students; Humans; Hydrogen Bonding; Hydrogen bonds; Hypertension; In-silico characterization; Inhibition; Inhibitory Concentration 50; Internal Medicine; Life sciences; Ligands; Metalloendopeptidases - antagonists & inhibitors; Metalloendopeptidases - chemistry; Metalloendopeptidases - metabolism; Molecular Dynamics Simulation; Molecular weight; Molegro virtual docker; Other; Protein Binding; Software; Structure-Activity Relationship; TSAR; ECE-1; Endothelin; In-silico characterization; Endothelin converting enzyme; Atherosclerosis; TSAR; Docking; Inhibition; Molegro virtual docker
• ISSN: 0010-4825; 1879-0534
• DOI: 10.1016/j.compbiomed.2011.12.013

Abstract Atherosclerosis is the primary cause of CAD and cerebrovascular disease. Endothelin (ET)-1 is a vasoconstrictive peptide implicated in Atherosclerosis pathology. Endothelin-converting enzyme (ECE) is a membrane metalloprotease that generates endothelin. Reported inhibitors of ECE-1 and their IC50 values were retrieved from literature and their structures were docked with the parent protein using the Molegro virtual docker. The obtained MolDock scores of each of the compounds are hereby reported and are subject to graphical analysis in conjunction with their respective IC50 values to characterize potent inhibitors. A search was then run in the ZINC database for compounds with similar properties. Potent inhibitors with higher Dock scores and better Ranking were isolated and are reported.