Detection of the Atherosclerotic PCSK9 gene Inhibitors Through in silico Method to Improve Targeted Therapy

Abstract

The PCSK9 is one of the most important marks for the evolution of therapeutic agents for atherosclerosis because its interaction with low-density lipoprotein receptors causes atherosclerosis. Protein-ligand interactions help us to understand the true mechanism of pharmacological action. This study seeks to identify the most powerful suppression options for PCSK9. Initially, the reported ACE inhibitors were included in pharmacophore modeling using PharmaGist. Next, ZINCPHARMER was used to screen the selected model against a ZINC database to identify putative drug candidates docked to the target protein to understand the interactions. The 10 best pharmacological candidates for PCSK9 with a binding energy of 9.8-8.2 kcal mol-1 were identified by molecular docking and their pharmacokinetic properties and oral bioavailability were evaluated. The (S) severalplant obtained chemicals have been discovered, including anti-hypersensitive drugs such as “Canadine, Hesperetin, and Labetalol”. According to Biochemistry, these compounds formed a stable “protein-ligand” complex. The (S) canadine PCSK9 complex had the lowest RMSD and was the most stable. Future in vitro studies could identify (S) canadin as a promising atherosclerosis inhibitor for the evolution of novel PCSK9 inhibitors.

Brazilin from Caesalpinia sappan L. as a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor: Pharmacophore-Based Virtual Screening, In Silico Molecular Docking, and In Vitro Studies

“…Figure 2 presents a visualization of the best molecular docking results between PCSK9 and herb-specific active compounds. The smaller binding affinity score indicates that the bond between the ligand and the receptor is stronger, and the bond between the compound and the receptor is said to be good if the value is less than −6.0 kcal/mol [ 29 , 34 , 35 ].…”

“…The prodomain and C-terminal domain of PCSK9 play a critical role in this interaction, which leads to increased plasma LDL-C levels and a higher risk of cardiovascular disease [ 28 ]. Out of all the available protein structures in the PDB database, PDB ID 6U26 [ 29 ] was selected as the final structure because of its high resolution (1.59 Å) and active site domains. The protein structure was separated from water molecules and native ligands using the BIOVIA application ( https://discover.3ds.com/discovery-studio ).…”