Minky Son
Chanin Park
Ayoung Baek
Shalini John
Keun Woo Lee
2013-01-29
<p>3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the conversion of HMG-CoA to mevalonate using NADPH and the enzyme is involved in rate-controlling step of mevalonate. Inhibition of HMGR is considered as effective way to lower cholesterol levels so it is drug target to treat hypercholesterolemia, major risk factor of cardiovascular disease. To discover novel HMGR inhibitor, we performed structure-based pharmacophore modeling combined with molecular dynamics (MD) simulation. Four HMGR inhibitors were used for MD simulation and representative structure of each simulation were selected by clustering analysis. Four structure-based pharmacophore models were generated using the representative structure. The generated models were validated used in virtual screening to find novel scaffolds for inhibiting HMGR. The screened compounds were filtered by applying drug-like properties and used in molecular docking. Finally, four hit compounds were obtained and these complexes were refined using energy minimization. These compounds might be potential leads to design novel HMGR inhibitor.</p>
https://doi.org/10.5281/zenodo.1333334
oai:zenodo.org:1333334
eng
Zenodo
https://doi.org/10.5281/zenodo.1333333
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
International Journal of Medical, Medicine and Health Sciences, 6.0(1), (2013-01-29)
Discovery of Human HMG-Coa Reductase Inhibitors Using Structure-Based Pharmacophore Modeling Combined with Molecular Dynamics Simulation Methodologies
info:eu-repo/semantics/article