IDENTIFICATION OF POSSIBLE MOLECULAR TARGETS OF POTENTIAL ANTI-PARKINSON DRUGS BY PREDICTING THEIR BINDING AFFINITIES USING MOLECULAR DOCKING TECHNIQUE

Objective: Mechanistic study of newly reported anti-Parkinson agents by molecular docking to predict possible target.Methods: Structures of newer drugs known anti-Parkinson agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using 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 AutoDock Vina (ADT) interface. ADT 1.5.6 software version was used for molecular docking study.Results: Various molecular targets were selected (D2/D3, D2, A2A, and MAO-B) and studied for Pardoprunox, Istradefylline, Rasagiline, and Bromocriptine. Pardoprunox, Istradefylline, and Bromocriptine had more affinity with their corresponding receptor with −6.9, −8.5, and −9.4 kcal/mol binding affinity, respectively, except Rasagiline, who has less affinity with its corresponding receptor (−6.4kcal/mol) and shown better affinity with 3pbl receptor (−6.7 kcal/mol).Conclusion: Pardoprunox, Istradefylline, and Bromocriptine were found to act on D2/D3 (3pbl), A2A (3pwh), and D2 (4yyw), respectively, whereas Rasagiline found to be act on D2/D3 (3pbl) receptor. The results help in prediction of mechanism and interaction to various Parkinson’s disease targets.

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

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s2.28587 ◽

2018 ◽

Vol 11 (14) ◽

pp. 76 ◽

Cited By ~ 1

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.

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Bioactive Antidiabetic Flavonoids from the Stem Bark of Cordia dichotoma Forst.: Identification, Docking and ADMET Studies

Molbank ◽

10.3390/m1234 ◽

2021 ◽

Vol 2021 (2) ◽

pp. M1234

Author(s):

Nazim Hussain ◽

Bibhuti Bhushan Kakoti ◽

Mithun Rudrapal ◽

Khomendra Kumar Sarwa ◽

Ismail Celik ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Mass Spectroscopy ◽

Column Chromatography ◽

Stem Bark ◽

Antidiabetic Activity ◽

Bark Extract ◽

Computational Studies ◽

Autodock Vina ◽

Online Tool

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3′,4′-tetrahydroxy-4-methoxyflavone-3-O-L-rhamnopyranoside and 5,7,3′-trihydroxy-4-methoxyflavone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal α-glucosidase and human pancreatic α-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

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

Jurnal e-Biomedik ◽

10.35790/ebm.v9i1.32361 ◽

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

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Pengaruh Minimisasi Energi MMFF94 dengan MarvinSketch dan Open Babel PyRx pada Penambatan Molekular Turunan Oksindola Tersubstitusi

ALCHEMY ◽

10.18860/al.v8i2.10481 ◽

2020 ◽

Vol 8 (2) ◽

pp. 33-40

Author(s):

Atika Umi Hanif ◽

Prima Agusti Lukis ◽

Arif Fadlan

Keyword(s):

Molecular Docking ◽

Drug Discovery ◽

Force Field ◽

Binding Affinity ◽

Energy Minimization ◽

In Silico ◽

Initial State ◽

Molecular Force ◽

Molecular Force Field ◽

Docking Energy

In silico technique is widely used for drug discovery because it can predict the conformation of ligands in protein macromolecules and it can calculate the binding affinity. The energy minimization is carried out to make the ligand more stable near the initial state during molecular docking process. The Merck Molecular Force Field (MMFF94) is one type of energy minimization process often used in organic compounds. The molecular docking of substituted oxindole derivatives on indoleamine macromolecules 2,3-dioxygenase (IDO-1, PDB: 2D0T) by MMFF94 minimization operated by MarvinSketch and Open Babel in PyRx showed different results. The binding affinity energy obtained was also quite different, but the ligands have the same conformation and bind the same residue with slightly different bond distances. Keywords: Molecular docking, energy minimization, substituted oxindole, Merck Molecular Force Field 94 Teknik in silico banyak digunakan untuk penemuan senyawa obat karena dapat memprediksi konformasi suatu ligan dalam makromolekul protein dan mampu menghitung nilai afinitas ikatan. Proses minimisasi energi dilakukan untuk menjadikan ligan lebih stabil mendekati keadaan awal selama penambatan molekular berlangsung. Merck Molecular Force Field (MMFF94) adalah salah satu jenis persamaan minimisasi energi yang sering digunakan pada senyawa organik. Hasil pengujian pengaruh minimisasi energi dengan MMFF94 menggunakan program MarvinSketch dan Open Babel dalam PyRx pada turunan oksindola tersubstitusi alkil terhadap makromolekul 2,3-dioxygenase indoleamine (IDO-1, PDB: 2D0T) menunjukkan hasil dengan nilai yang berbeda. Energi afinitas ikatan yang didapatkan juga cukup berbeda, namun ligan memiliki konformasi yang sama dan mengikat residu yang sama dengan jarak ikatan yang sedikit berbeda. Kata kunci: Penambatan molekular, minimisasi energi, oksindola tersubstitusi, Merck Molecular Force Field 94

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Design of more potent quinazoline derivatives as EGFRWT inhibitors for the treatment of NSCLC: a computational approach

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-021-00279-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Muhammad Tukur Ibrahim ◽

Adamu Uzairu ◽

Sani Uba ◽

Gideon Adamu Shallangwa

Keyword(s):

Lung Cancer ◽

Molecular Docking ◽

Binding Affinity ◽

Positive Control ◽

Computational Approach ◽

Tyrosine Kinase Receptor ◽

Binding Affinities ◽

Binding Interaction ◽

Pharmacokinetic Properties ◽

Inhibitory Activities

Abstract Background Lung cancer remains the leading and deadly type of cancer worldwide. It was estimated to account for about 25% of the 7 million people that died as a result of cancer-related issues/mortality every year in the world. Non-small cell lung cancer (NSCLC) is the lethal/deadly class of lung cancer with nearly 1.5 million reported cases and less than 20% survival rate. Therefore, it becomes necessary to explore more effective NSCLC drugs. Result A computational approach was employed here to design ten new EGFRWT inhibitors using compound 18 as a template for the design identified with the best binding affinity and good pharmacokinetic properties previously reported in our work. The modeled inhibitory activities of these newly designed EGFRWT inhibitors (range from 7.746966 to 11.09261) were better than that of the hit compound with pIC50 of 7.5639 and gefitinib the positive control with pIC50 of 5.879426. The ligand-binding interaction between these newly designed EGFRWT inhibitors and the EGFR tyrosine kinase receptor as shown in Table 3 was investigated and elucidated using molecular docking protocol. Based on the molecular docking results, the binding affinities of these newly designed EGFRWT inhibitors were found to be between − 8.8 and − 9.5 kcal/mol. The designed compound SFD10 has the highest binding affinity of − 9.5 kcal/mol followed by compound SFD8 (with a binding affinity of − 9.3 kcal/mol), then by compound SFD9 and 4 (each with a binding affinity of − 9.3 kcal/mol). None of them was found to have more than one violation of the filtering criterion used in this study thereby showing good ADMET properties. Conclusion The modeled inhibitory activities and binding affinities of these newly designed EGFRWT inhibitors were found to be higher than that of the template compound and the control (gefitinib) used in this research. They were also seen to be non-toxic with good pharmacokinetic properties.

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Molecular Docking Analysis Of Some Phytochemicals On Two SARS-CoV-2 Targets: Potential Lead Compounds Against Two Target Sites of SARS-CoV-2 Obtained from Plants

10.1101/2020.03.31.017657 ◽

2020 ◽

Cited By ~ 3

Author(s):

Amaka Ubani ◽

Francis Agwom ◽

Oluwatoyin RuthMorenikeji ◽

Shehu Nathan ◽

Pam Luka ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Potential Candidate ◽

Binding Affinities ◽

Protein Targets ◽

Docking Analysis ◽

Lead Compounds ◽

Target Sites ◽

Antiviral Activities ◽

Molecular Docking Analysis

AbstractCOV spike (S) glycoprotein and Mpro are two key targets that have been identified for vaccines and drug development against the COVID-19 disease. Virtual screening of some compounds of plants origin that have shown antiviral activities were carried out on the two targets, 6lu7 and 6vsb by docking with the PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for 6lu7 and 6vsb as well as Chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of Physicochemical properties and toxicity respectively. The docking results revealed that scopodulcic acid and dammarenolic acid had the best binding affinity on the s-glycoprotein and Mpro protein targets respectively. Silybinin also demonstrated a good binding affinity to both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS COV2 with likelihood of having a multitarget activity.

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Bioactive Flavonoids from the Stem Bark of Cordia dichotoma Forst.: Identification, Docking and ADMET Studies

10.20944/preprints202105.0171.v1 ◽

2021 ◽

Author(s):

Nazim Hussain ◽

Bibhuti Bhushan Kakoti ◽

Mithun Rudrapal ◽

Khomendra Kumar Sarwa ◽

Ismail Celik ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Mass Spectroscopy ◽

Stem Bark ◽

Antidiabetic Activity ◽

Bark Extract ◽

Computational Studies ◽

Autodock Vina ◽

Online Tool ◽

Alpha Glucosidase

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

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IDENTIFICATION OF NOVEL 5-STYRYL-1,2,4-OXADIAZOLE/TRIAZOLE DERIVATIVES AS THE POTENTIAL ANTI-ANDROGENS THROUGH MOLECULAR DOCKING STUDY

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i10.13844 ◽

2016 ◽

Vol 8 (10) ◽

pp. 72 ◽

Cited By ~ 3

Author(s):

Paranjeet Kaur ◽

Gopal L. Khatik

Keyword(s):

Molecular Docking ◽

Androgen Receptor ◽

Binding Affinity ◽

Docking Study ◽

Molecular Structures ◽

The Novel ◽

Autodock Vina ◽

Molecular Docking Study ◽

Triazole Derivatives ◽

Better Than

Objective: To identify the novel and simple bioactive antiandrogens, that can overcome to side effects as well as drug resistance.Methods: The AutoDock Vina (ADT) 1.5.6 software is used for molecular docking purposes. The molecular structures were drawn in ChemBiodraw ultra and by the help of ChemBiodraw 3D, all structures were energy minimized by MM2 method and converted to pdb extension file which is readable at the ADT interface.Results: Total ten compounds from both series were shown better binding affinity than R-bicalutamide including oxadiazole and triazole series. Among these pk42 and pk46 were studied in-depth which showed best binding affinity to the androgen receptor. The cis-isomers were found better than their trans-isomer.Conclusion: Novel 5-styryl-1,2,4-oxadiazole/triazole derivatives were studied through molecular modeling using Autodock Vina. The potent compounds which showed better binding affinity than R-bicalutamide like pk24 and 46 were further analyzed for their interactions. The conformational effect also found significant in binding to the androgen receptor.

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Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽

10.3390/molecules26040809 ◽

2021 ◽

Vol 26 (4) ◽

pp. 809 ◽

Cited By ~ 3

Author(s):

Md. Zia Uddin ◽

Arkajyoti Paul ◽

Ahmed Rakib ◽

Saad Ahmed Sami ◽

Shafi Mahmud ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Serotonin Receptor ◽

Computational Study ◽

Biological Activities ◽

Binding Affinities ◽

In Silico Studies ◽

Cox 2 ◽

Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

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HIGH-THROUGHPUT SCREENING AND DYNAMIC STUDIES OF SELECTED COMPOUNDS AGAINST SARS-COV-2

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2022v14i1.43105 ◽

2022 ◽

pp. 251-260

Author(s):

RATUL BHOWMIK ◽

RANAJIT NATH ◽

SAMEER SHARMA ◽

RATNA ROY ◽

RIYA BISWAS

Keyword(s):

Drug Delivery ◽

Molecular Docking ◽

Binding Affinity ◽

High Throughput Screening ◽

In Silico Analysis ◽

Inhibitory Effect ◽

Binding Affinities ◽

Pubchem Database ◽

Potential Inhibitors ◽

3Cl Protease

Objective: This study was aimed to analyze the inhibitory effect of the drugs used in nanocarrier as well as nanoparticles formulation based drug delivery system selected from PubChem database literature against 3CLpro (3C-like protease) receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by implementing several in silico analysis techniques. Methods: This paper detailed a molecular docking-based virtual screening of 5240 compounds previously utilized in nanoparticle and nanocarrier drug delivery systems utilizing AutoDock Vina software on 3CL protease to discover potential inhibitors using a molecular docking technique. Results: According to the results of the screening, the top two compounds, PubChem Id 58823276 and PubChem Id 60838 exhibited a high affinity for the 3CL protease binding region. Their binding affinities were-9.6 and-8.5 kJ/mol, indicating that they were tightly bound to the target receptor, respectively. These results outperformed those obtained using the co-crystallized native ligand, which exhibited a binding affinity of-7.4 kJ/mol. PubChem Id 60838, the main hit compound in terms of both binding affinity and ADMET analysis, displayed substantial deformability after MD simulation. As a result of the VS and molecular docking techniques, novel 3CL protease inhibitors from the PubChem database were discovered using the Lipinski rule of five and functional molecular contacts with the target protein, as evidenced by the findings of this work. Conclusion: The findings suggest that the compounds discovered may represent attractive opportunities for the development of COVID-19 3CLpro inhibitors and that they need further evaluation and investigation.

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