scholarly journals Identification of a novel inhibitor for the Bromodomain (BRD4) through a receptor-based drug discovery approach

2020 ◽  
Vol 11 (3) ◽  
pp. 4359-4364
Author(s):  
Arivukkarasi Varadharajan ◽  
Raman Rajeshkumar ◽  
Chandrasekar MJN
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Molecular Level ◽  
Autodock Vina ◽  
Rule Violation ◽  
Docking Analysis ◽  
Novel Target ◽  
The Right ◽  
Almost All ◽  
Derivatives Of

Recently, the demands on the drug discovery process have increased drastically because of the need to apprehend a novel target which might be both pertinent to cause disease and chemically tractable. The emergence of bioinformatics and computer strategies have given room to analyse conditions at the molecular level. The present work was to perform a molecular docking analysis and ADMET study of different δ-carboline derivatives with bromodomain (BRD4) receptor using receptor-based drug discovery approach. Based on the literature, 60 compounds were designed and subjected to molecular docking for the inhibition of brd4 receptor. The results showed that Compound 34 received the highest binding affinity with BRD4 receptor. Hence eight compounds were selected based on docked pose determined using AutoDock/Vina with the minimal energy of above -5.1. Then ADMET study was carried, in that, all the eight compounds had middle to high BBB permeability. During metabolism, all compounds except compounds 37, 42 and 47 showed no inhibition of CYP2C99 in the liver. Analysis of drug-likeness profile showed almost all compounds eligible in CMC rule, violation rule of CMC, MDDR rule with the value of 1 and violations of WDI showed 0 value. Such findings strongly implied that derivatives of δ-carboline could serve as lead molecules to inhibit BRD4, and this could lead to the future development of the right candidate for cancer research.

scholarly journals Molecular Docking Senyawa Gingerol dan Zingiberol pada Tanaman Jahe sebagai Penanganan COVID-19

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Belinda D. P. M. Ratu ◽  
Widdhi Bodhi ◽  
Fona Budiarso ◽  
Billy J. Kepel ◽  
. Fatimawali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Amino Acid Residues ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Main Protease ◽  
Docking Method ◽  
Pubmed Database ◽  
Almost All ◽  
The Impact

Abstract: COVID-19 is a new disease. Many people feel the impact of this disease. There is no definite cure for COVID-19, so many people use traditional medicine to ward off COVID-19, including ginger. This study aims to determine whether there is an interaction between compounds in ginger (gingerol and zingiberol) and the COVID-19’s main protease (6LU7). This study uses a molecular docking method using 4 main applications, namely Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, and Open Babel GUI. The samples used were gingerol and zingiberol compounds in ginger plants downloaded from Pubchem. The data used in this study used Mendeley, Clinical Key, and PubMed database. The study showed that almost all of the amino acid residues in the gingerol compound acted on the 6LU7 active site, whereas the zingiberol did not. The results of the binding affinity of ginger compounds, both gingerol and zingiberol, do not exceed the binding affinity of remdesivir, a drug that is widely researched as a COVID-19 handling drug. In conclusion, gingerol and zingiberol compounds in ginger can’t be considered as COVID-19’s treatment.Keywords: molecular docking, gingerol, zingiberol Abstrak: COVID-19 merupakan sebuah penyakit yang baru. Banyak masyarakat yang merasakan dampak dari penyakit ini. Belum ada pengobatan pasti untuk menyembuhkan COVID-19, sehingga banyak masyarakat yang menggunakan pengobatan tradisional untuk menangkal COVID-19, termasuk jahe. Penelitian ini bertujuan untuk mengetahui apakah ada interaksi antara senyawa pada jahe (gingerol dan zingiberol) dengan main protease COVID-19 (6LU7). Penelitian ini menggunakan metode molecular docking dengan menggunakan 4 aplikasi utama, yaitu Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, dan Open Babel GUI. Sampel yang digunakan yaitu senyawa gingerol dan zingiberol pada tanaman jahe yang diunduh di Pubchem. Data yang digunakan dalam penelitian ini menggunakan database Mendeley, Clinical Key, dan PubMed. Penelitian menunjukkan bahwa hampir semua residu asam amino pada senyawa gingerol bekerja pada sisi aktif 6LU7, sedangkan tidak demikian pada zingiberol. Hasil binding affinity senyawa jahe, baik gingerol maupun zingiberol tidak  melebihi binding affinity remdesivir, obat yang banyak diteliti sebagai obat penanganan COVID-19. Sebagai simpulan, senyawa gingerol dan zingiberol pada tanaman jahe tidak dapat dipertimbangkan sebagai penanganan COVID-19Kata Kunci: molecular docking, gingerol, zingiberol

scholarly journals Molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein

2020 ◽  
Vol 16 (11) ◽  
pp. 937-941
Author(s):  
Ramajayam Govindan ◽  
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Docking Analysis ◽  
Molecular Binding ◽  
Different Types ◽  
Molecular Docking Analysis

The MUC1 oncoprotein is known to be linked with different types of cancer. Therefore, it is of interest to document the molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein. We report the structure based molecular binding features compounds such as amrinone, ethambutol, pyrazinamide and vasicoline the MUC1 oncoprotein for further consideration in drug discovery.

scholarly journals Synthesis and Biological Activity of Triazole Derivatives of Osajin

2021 ◽  
Vol 33 (6) ◽  
pp. 1267-1272
Author(s):  
L.V. Ramana ◽  
K.M.Ch. Appa Rao ◽  
M. Suri Appa Rao ◽  
Ch. Venkata ramanaiah ◽  
G. Nageswara Rao
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Parent Compound ◽  
Docking Studies ◽  
Strong Interactions ◽  
Spectroscopic Techniques ◽  
Docking Analysis ◽  
Hela Cell Lines ◽  
In Silico Molecular Docking ◽  
Derivatives Of

In the present study, osajin-1,2,3-triazole hybrids were designed, synthesized and evaluated for their anti-proliferative activity against MCF-7, PC-3 and Hela cell lines. Many of the synthesized hybrid derivatives were found potent than the parent compound, osajin (1). All the semi-synthesized derivatives (3a-j) were characterized by using mass and NMR spectroscopic techniques. Among the newly synthesized compounds, 3c, 3d, and 3e were shown promising activities against the tested cell lines compared with doxorubicin standard. In addition, molecular docking studies of the synthesized compounds have shown a good correlation with in silico molecular docking analysis by exhibiting strong interactions with the inhibitor HERA-protein.

scholarly journals Computational Molecular Docking Analysis and Visualisation of Anthocyanins for Anticancer Activity

2021 ◽  
Vol 8 (1) ◽  
pp. 154-161
Author(s):  
Mahankali Sravani ◽  
Akash Kumaran ◽  
Aditi Tulshiram Dhamdhere ◽  
Nachimuthu Senthil Kumar
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Complex Compounds ◽  
Potential Drug ◽  
Drug Molecule ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Almost All ◽  
Molecular Docking Analysis ◽  
Computational Molecular Docking

Various invitro and computational methods were implemented to evaluate the anticancer potential of anthocyanidins, namely cyanidin, malvidin, delphinidin, peonidin, pelargonidin, and petunidin. These anthocyanidins were docked with CDK-2, CDK-6 and IGF-1R kinase proteins. Additionally, known inhibitors (KIs) such as SU9516, Palbociclib, OSI-906 are compared with their respective macromolecules, including, CDK-2, CDK-6 and IGF-1R kinase, in to compare results of the study based on Lipinski rule of 5.  The Auto Dock Tool (Autodock 4) was used for molecular docking, and the docked complex compounds were visualised and interpreted using the Bio via Discovery Studio 2020 client. The Docking results obtained showed a very good inhibitory binding to almost all the selected cancer proteins, and these compounds might be a potential drug molecule.

scholarly journals Comparative Antibacterial Analysis of the Anthraquinone Compounds Based on the AIM Theory and Molecular Docking Analysis

2021 ◽  
Author(s):  
Yanjiao Qi ◽  
Mingyang Wang ◽  
Bo Zhang ◽  
Yue Liu ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energies ◽  
Hydrogen Atoms ◽  
Docking Analysis ◽  
Comprehensive Comparison ◽  
Molecular Potentials ◽  
Almost All ◽  
Atoms In Molecules Theory ◽  
Hydroxyl Hydrogen ◽  
Present Text

Abstract Hydroxyanthraquinones and anthraquinone glucoside derivatives are always considered as the active antibacterial components. In the present text, a comprehensive comparison and analysis of these compounds were performed for their structure characteristics and antibacterial effect by applying quantum chemical calculations, atoms in molecules theory and molecular docking procedure. The molecular geometric configuration, electrostatic potential, the frontier orbital energies and topological properties were analyzed. Once glucose ring is introduced into the hydroxyanthraquinone rings, almost all of the positive molecular potentials are distributed among the hydroxyl hydrogen atoms of the glucose rings. The anthraquinone glucoside compounds have generally higher intermolecular binding energies than the corresponding aglycones due to the strong interaction between the glucose rings and the surrounding amino acids. Once glucoside ring is introduced into the emodin, low electron density ρ(r) and positive Laplacian value of the O-H bond are the evidences of the highly polarized and covalently decreased bonding interactions. The type of carboxyl, hydroxyl, hydroxylmethyl groups on phenyl ring and the substituent glucose rings are important to the interactions with the topoisomerase type II enzyme DNA gyrase B.

scholarly journals A COMPARATIVE STUDY OF STEREOCHEMICAL EFFECTS OF ANTI-PROSTATE AGENTS BY MOLECULAR DOCKING

2018 ◽  
Vol 11 (14) ◽  
pp. 76 ◽  
Author(s):  
Oluwaseun S Osanyinpeju ◽  
Roqia Bashary ◽  
Amit Mittal ◽  
Manish Vyas ◽  
Surendra Kumar Nayak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Docking ◽  
Comparative Study ◽  
Binding Affinity ◽  
Energy Minimization ◽  
Receptor Protein ◽  
Autodock Vina ◽  
Androgen Receptor Protein ◽  
The Right ◽  
3D Software

Objective: A comparative study of anti-prostate agents to investigate the stereochemical influences on binding affinity by molecular docking.Methods: Structures of enantiomers (R and S stereoisomers) for known anti-prostate cancer (PCa) agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using the ChemBioDraw 3D software in which they were subjected to energy minimization using the MM2 method and then saved as PDB extension files which can be accessed using the ADT interface. AutoDock Vina (ADT) 1.5.6 software version was used for molecular docking study.Results: A total of 12 different anti-PCa agents were selected and drawn including well-known drug R-bicalutamide. All molecules showed the binding affinity with respect to the nature of stereochemistry. R-stereoisomers showed better interaction as well as binding affinity toward 1z95 (mutated androgen receptor protein involved in the progression of PCa) whereas their S-stereoisomers were found inferior in comparison.Conclusion: This study showed that CB1-R and R-bicalutamide (with R-stereochemistry) were better in binding affinity comparative to their counterpart CB1-S and S-Bicalutamide (with S-stereochemistry). All the selected anti-PCa agents were showing the effect of stereochemical center; therefore, we must choose the right kind of stereochemistry while planning to develop the newer anti-PCa agents.

scholarly journals Exploring Molecular Docking algorithm for Lung Cancer Drug Discovery – A Case Study with RET Protein

2020 ◽  
Vol 11 (4) ◽  
pp. 5198-5205
Author(s):  
Shristi Chaturvedi ◽  
Megha Vinod P I ◽  
Gargi Mosha ◽  
Ramanathan K
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Drug Discovery ◽  
Cancer Drug ◽  
Autodock Vina ◽  
Cancer Drug Discovery ◽  
Docking Algorithm ◽  
Autodock 4.0 ◽  
Source Of Information

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths across the globe.1.33% of all NSCLC cases occur due to an alteration in RET protein. Commonly occurring RET fusion partners include KIF5B, CCDC6, NCOA4, and TRIM33. Numerous multikinase inhibitors are active against rearranged RET. However, mutations in the RET-fusion protein can result in adverse effects in terms of drug resistance against NSCLC. In this context, molecular docking algorithm is certainly important to support the drug discovery pipelines. However, availability of huge number of algorithms in the literature limits the researchers to proceed further in drug discovery development. Thus, the present study focuses on finding the best docking algorithm among ArgusLab, PatchDock, AutoDock 4.0 and AutoDock Vina for drug discovery process against RET fusion cancers using Pearson’s correlation coefficient. We believe that our study will be a valuable source of information for carrying out further computational studies on RET fusion cancer, both mutant and wild type.

scholarly journals Molecular Docking: Shifting Paradigms in Drug Discovery

2019 ◽  
Vol 20 (18) ◽  
pp. 4331 ◽  
Author(s):  
Luca Pinzi ◽  
Giulio Rastelli
Keyword(s):  
Artificial Intelligence ◽  
Molecular Docking ◽  
Drug Discovery ◽  
Chemical Structure ◽  
Molecular Level ◽  
A Priori ◽  
Drug Repurposing ◽  
Large Molecules ◽  
Structure Activity ◽  
Target Fishing

Molecular docking is an established in silico structure-based method widely used in drug discovery. Docking enables the identification of novel compounds of therapeutic interest, predicting ligand-target interactions at a molecular level, or delineating structure-activity relationships (SAR), without knowing a priori the chemical structure of other target modulators. Although it was originally developed to help understanding the mechanisms of molecular recognition between small and large molecules, uses and applications of docking in drug discovery have heavily changed over the last years. In this review, we describe how molecular docking was firstly applied to assist in drug discovery tasks. Then, we illustrate newer and emergent uses and applications of docking, including prediction of adverse effects, polypharmacology, drug repurposing, and target fishing and profiling, discussing also future applications and further potential of this technique when combined with emergent techniques, such as artificial intelligence.

Sign in / Sign up

Export Citation Format

Share Document