Dataset Information

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.

SUBMITTER: Rathod S

PROVIDER: S-EPMC9835631 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Rathod Sanket S Shinde Ketaki K Porlekar Jaykedar J Choudhari Prafulla P Dhavale Rakesh R Mahuli Deepak D Tamboli Yasinalli Y Bhatia Manish M Haval Kishan P KP Al-Sehemi Abdullah G AG Pannipara Mehboobali M

ACS omega 20221221 1

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 ag ...[more]

PMID: 36643495

Similar Datasets

Project description:Dengue poses a persistent and widespread threat with no effective antiviral drug available till now. Several inhibitors have been developed by targeting the viral non-structural proteins including methyl transferase (NS5) of the dengue virus with possible therapeutic values. In this work, virtual screening, molecular docking, molecular dynamics simulations (200 ns), and assessments of free energy changes have been carried out to identify potential candidates from a database of flavonoids (ca. 2000) that may have good curative potential from the disease. The binding affinity of flavonoids, namely Genistein-7-glucoside (FLD1), 6'-O-Acetylgenistin (FLD2), 5,6-dihydroxy-2-(4-hydroxyphenyl)-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-yl]oxychromen-4-one (FLD3), Glucoliquiritigenin (FLD4), and Chrysin-7-O-glucoronide (FLD5) showed the binding affinities of -10.2, -10.2, -10.1, -10.1, -9.9 kcal/mol, respectively, and possessed better values than that of the native ligand (-7.6 kcal/mol) and diclofenac sodium (-7.3 kcal/mol). Drug-likeness of the top five flavonoids were acceptable and no end-point toxicity was hinted by ADMET predictions. The stability of the protein-ligand complexes was accessed from 200 ns molecular dynamics simulations in terms of various geometrical parameters; RMSD, RMSF of residues, Rg, SASA, H-bond, and RPDF. The binding free energy changes of these adducts were calculated by the MM/PBSA solvation model with negative values (from -38.01±7.53 to -17.75±11.03 kcal/mol) indicating the sustained spontaneity of the forward reaction and favorability of the product formation. The geometrical and thermodynamic parameters inferred that the flavonoids could bind at the orthosteric site of the target protein of DENV-2 and could inhibit its functioning, possibly, resulting in the prevention of the disease. Overall, this study highlights the anti-DENV activity of five flavonoids, positioning them as promising candidates for further development as antiviral agents against dengue infection.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets