Computational Exploration of Anti-cancer Potential of Flavonoids against Cyclin-Dependent Kinase 8: An In Silico Molecular Docking and Dynamic Approach

Abstract

Over the centuries, cancer has been considered one of the significant health threats. It holds the position in the list of deadliest diseases over the globe. In women, breast cancer is the most common among many cancers and is the second most common cancer all over the world, while lung cancer is the first. Cyclin-dependent kinase 8 (CDK8) has been identified as a critical oncogenic driver that is found in breast cancer and associated with tumor progression. Flavonoids were virtually screened against CDK8 using molecular docking, drug-likeness, ADMET prediction, and a molecular dynamics (MD) simulation approach to determine the potential flavonoid structure against CDK8. The results indicated that ZINC000005854718 showed the highest negative binding affinity of −10.7 kcal/mol with the targeted protein and passed all the drug-likeness parameters. Performed molecular dynamics simulation showed that docked complex systems have good conformational stability over 100 ns in different temperatures (298, 300, 305, 310, and 320 K). The comparison between calculated binding free energy via MM/PB(GB)SA methods and binding affinity calculated via molecular docking suggested tight binding of ZINC000005854718 with targeted protein. The results concluded that ZINC000005854718 has drug-like properties with tight and stable binding with the targeted protein.

Synthesis, Characterization, In Silico DFT, Molecular Docking, and Dynamics Simulation Studies of Phenylhydrazono Phenoxyquinolones for Their Hypoglycemic Efficacy

“…Docking studies were conducted using the AutoDock Vina module in PyRx 0.8 with a maximized grid spacing. ,,, Initially, protein structures obtained from the RCSB Protein Data Bank were thoroughly cleaned, with prior ligands and water molecules. Polar hydrogen atoms were added, and the structures were optimized using BIOVIA Discovery Studio, ensuring accurate tautomeric states . Following energy minimization, ligand and protein structures were chosen for the docking study in Vina Wizard, with a maximized grid box covering the entire protein.…”

“…Polar hydrogen atoms were added, and the structures were optimized using BIOVIA Discovery Studio, ensuring accurate tautomeric states. 61 Following energy minimization, ligand and protein structures were chosen for the docking study in Vina Wizard, with a maximized grid box covering the entire protein. Parameters such as exhaustiveness at eight and the number of modes at nine were configured for the study.…”

Evaluation of novel pyridoxal isonicotinoyl hydrazone (PIH) derivatives as potential anti‐tuberculosis agents: An in silico investigation

“…The ProSA‐web server was employed to evaluate z‐scores, taking into account data from X‐ray crystallography (light blue) or NMR spectroscopy (dark blue). Furthermore, the ProSA‐web energy plot was considered for assessing local model quality [76].…”

Exploring the potential of fluoro‐flavonoid derivatives as anti‐lung cancer agents: DFT, molecular docking, and molecular dynamics techniques

“…Compared to the many experimental studies, only a limited number of in silico studies have been conducted on flavonoid and its derivatives [35][36][37][38][39]. Dolatkhan et al [36] studied a series of 4H-chromone-1,2,3,4-tetrahydro pyrimidine-5-carboxylates products, and the in silico results indicated that these have no toxic effects, are potential antileukemic agents.…”

“…Dolatkhan et al [36] studied a series of 4H-chromone-1,2,3,4-tetrahydro pyrimidine-5-carboxylates products, and the in silico results indicated that these have no toxic effects, are potential antileukemic agents. Recently, Rathod et al [37] used in silico docking and molecular dynamics to explore flavonoids for possible anti-cancer activities against cyclin-dependent kinase 8 (CDK8). Their study shows flavonoid complexes possess many dynamic properties, such as high stability, significant binding energy, and fewer conformation fluctuations [38].…”