scholarly journals Simulasi Docking Molekuler Senyawa Potensial Tanaman Justicia Gendarussa Burm.f. Sebagai Antidiabetes

2020 ◽  
Vol 48 (2) ◽  
pp. 117-122
Author(s):  
Rosa Adelina
Keyword(s):  
Hydrogen Bonding ◽  
Molecular Docking ◽  
Binding Energy ◽  
Mechanism Of Action ◽  
In Silico ◽  
Research Method ◽  
Natural Compounds ◽  
Reference Drug ◽  
Energy Score

Abstract Indonesia has various natural compounds that are potential as antidiabetics but the mechanism of action was not yet known in detail, one of them is Justicia gendarussa. Justicia gendarussa is known as Gandarusa contains kaempferol and naringenin. In this study, the two compounds were simulated with glucokinase enzyme using a glibenclamide as a standard reference drug to determine their potential action as an antidiabetic. The research method was carried out using molecular docking computation simulation (in silico). The results showed the binding energy scores of glibenclamide, naringenin, and kaempferol to glucokinase enzymes are -22.0917; -22,1866; and -22,6328 kcal/mol, respectively. The hydrogen bonding plays in binding the enzyme. These results showed the binding energy score was not different significantly. Thus, naringenin and kaempferol had the same antidiabetic potential as glibenclamide. Keywords: Justicia gendarussa, antidiabetes, molecular docking, naringenin, kaempferol Abstrak Berbagai senyawa alam Indonesia berpotensi sebagai antidiabetes namun belum diketahui mekanisme aksinya secara rinci, salah satu contohnya Justicia gendarussa Burm.f.. Tanaman Justicia gendarussa yang dikenal baik dengan nama Gandarusa, mengandung kaempferol dan naringenin. Pada penelitian ini, kedua senyawa disimulasikan terhadap enzim glukokinase menggunakan senyawa pembanding glibenklamid yang merupakan obat referensi untuk mengetahui potensinya sebagai antidiabetes. Metode penelitian dilakukan menggunakan simulasi komputasi docking molekuler (in silico). Hasil docking molekuler menunjukkan skor energi ikatan glibenklamid, naringenin dan kaempferol terhadap enzim glukokinase masing-masing sebesar -22,0917; -22,1866 ; dan -22,6328 kkal/mol. Ikatan yang berperan adalah ikatan hydrogen. Hasil penelitian menunjukkan nilai skor energi ikatan yang tidak berbeda signifikan. Dengan demikian naringenin dan kaempferol memiliki potensi sebagai antidiabetes yang sama dengan glibenklamid. Kata kunci: Justicia gendarussa, antidiabetes, docking molekuler, naringenin, kaempfero

scholarly journals MOLECULAR DOCKING TERPINEN-4-OL SEBAGAI ANTIINFLAMASI PADA ATEROSKLEROSIS SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 221
Author(s):  
N. M. P. Susanti ◽  
N. P. L. Laksmiani ◽  
N. K. M. Noviyanti ◽  
K. M. Arianti ◽  
I K. Duantara
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Endothelial Dysfunction ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Inflammatory Process ◽  
Mapk Pathway ◽  
Chronic Inflammatory Disease ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

Atherosclerosis is a chronic inflammatory disease that begins with endothelial dysfunction, it caused fat accumulation and plaque growth in the inner arteries walls. Endothelial dysfunction will activate the Mitogen Activated Protein Kinase (MAPK) pathway involving ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, as well as the Nuclear Factor Kappa B (NF-kB) pathway involving IKK proteins. Terpinen-4-ol is constituent found in the bangle rhizome. The purpose of this study were to determine the affinity and mechanisms of terpinen-4-ol against ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins as anti-inflammatory in atherosclerosis performed using molecular docking method. The study was conducted exploratively with several steps such as preparation and optimization of terpinen-4-ol structure, preparation of 3D ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, validation method of molecular docking, and docking terpinen-4-ol in these proteins. The docking result are assessed from the binding energy and hydrogen bonds formed between terpinen-4-ol and proteins. The smaller value of binding energy terpinen-4-ol with target proteins showed the complex that form more stable. The result showed that terpinen-4-ol and has activity in inhibiting the inflammatory process because it is able to disturb ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins with respective bond energy values -5,12; -5,24; -5,08; -5,88; and -4,99 Kcal/mol. The molecular mechanism in inhibiting the activity of ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins is through the formation of hydrogen bonds in these proteins. These results show that terpinen-4-ol have the potential to inhibit inflammatory process and the formation of atherosclerotic plaque can be obstructed. Keywords : atherosclerosis, terpinen-4-ol, molecular docking, in silico

scholarly journals AKTIVITAS DARI KUERSETIN SEBAGAI AGEN PENCERAH KULIT SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 207
Author(s):  
K. D. Adnyani ◽  
L. W. E. Lestari ◽  
H. Prabowo ◽  
P. A. I. A. Siaka ◽  
N. P. L. Laksmiani
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Target Protein ◽  
Related Protein ◽  
Skin Whitening ◽  
Whitening Agent ◽  
Docking Method ◽  
Tyrosinase Related Protein ◽  
Molecular Docking Method

Increasing melanogenesis process causes excessive melanin synthesis resulting in darkening of the skin color. The melanogenesis process requires mealnogenesis enzymes, one of which is tyrosinase-related protein 1. One of the flavonoid compounds that has the potential as a skin lightening agent is quercetin. The antioxidant activity of quercetin plays a very important role in antimelanogenesis. This study aims to determine the affinity and molecular mechanism of quercetin on the target protein tyrosinase-related protein 1 using in silico molecular docking method. Molecular docking is carried out through stages including optimization of the structure of quercetin compounds, preparation of the target protein tyrosinase-related protein 1, validation of the molecular docking method, and docking of quercetin on the tyrosinase-related protein 1. Docking of quercetin with tyrosinase-related protein 1 produces binding energy values of -7.81 kcal/mol, while docking of native ligand with tyrosinase-related protein 1 produces binding energy values of -5.39 kcal/mol. Quercetin has a strong affinity for tyrosinase-related protein 1 which is indicated by the binding energy from the docking results. Quercetin has activity as a skin whitening agent with in silico test with molecular mechanisms through inhibition of the activity of tyrosinase-related protein 1 enzyme.  Keywords: skin whitening agent, in silico, quercetin, tyrosinase-related protein 1

Antiplasmodial Biodereplication Based on Highly Efficient Methods

2020 ◽  
Author(s):  
Pedro Vásquez-Ocmín ◽  
Jean-François Gallard ◽  
Anne-Cécile Van Baelen ◽  
Karine Leblanc ◽  
Sandrine Cojean ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Data Mining ◽  
Molecular Docking ◽  
Mechanism Of Action ◽  
In Silico ◽  
Binding Assay ◽  
Antimalarial Drugs ◽  
Heme Binding ◽  
Molecular Networking ◽  
In Silico Modeling

We propose a biodereplication method using mass spectrometry and combining the classical dereplication approach with the predominant mechanism of action of antimalarial drugs. The method encompasses a biomimetic heme binding assay (heme adducts detection by MS), molecular networking for quick data mining, CPC for extract fractionation and compounds isolation and in silico modeling of heme adducts by molecular docking.

Pharmacological study of A3 Adenosine receptor agonist (AB Meca) in xenograft lung cancer model in mice through in silico and in vivo approach: Targeting TNF-α

2021 ◽  
Vol 18 ◽  
Author(s):  
Nilay Solanki ◽  
Leena Patel ◽  
Shaini Shah ◽  
Ashish Patel ◽  
Swayamprakash Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Energy ◽  
Adenosine Receptor ◽  
In Silico ◽  
Human Lung Cancer ◽  
A3ar Agonist ◽  
Adenosine Receptor Agonist ◽  
Tnf Α

Background: Lung cancer is the leading cause of mortality in India. Adenosine receptor (AR) has emerged as a novel cancer-specific target. A3AR levels are upregulated in various tumor cells, which may mean that the specific AR may act as a biological marker and target specific ligands leading to cell growth inhibition. Aim: Our aim was to study the utility of the TNF-α agonist, AB MECA, by in silico (molecular docking) and in vitro (human cancer cells in xenografted mice) studies. Method: Molecular docking on the AB-meca and TNF-α was performed using AutoDock. A549 Human lung cancer 2 ×106 cells per microliter per mouse injected via intrabronchial route. Rat TNF-α level was assessed by ELISA method. Results: AB Meca's predicted binding energy (beng) with TNF-α was 97.13 kcal/mol, and the compatible docking result of a small molecular inhibitor with TNF-α native ligand beng was 85.76 kcal/mol. In vivo, a single dose of lung cancer cell A549 is being researched to potentiate tumor development. Doxorubicin and A3AR agonist therapies have lowered TNF-alpha levels that were associated with in silico function. The A3AR Agonist myeloprotective effect was also found in groups treated with doxorubicin. Conclusion: AB MECA’s higher binding energy (beng) with TNF-α mediated reduction of tumor growth in our lung cancer in vivo model suggests that it may be an effective therapy for lung cancer.

Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach

2020 ◽  
Vol 11 (1) ◽  
pp. 7981-7993
Keyword(s):  
Molecular Docking ◽  
Allium Cepa ◽  
In Silico ◽  
Treatment Options ◽  
Natural Compounds ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Main Protease

The infection of the global COVID-19 pandemic and the absence of any possible treatment options warrants the use of all available resources to find effective drugs against this scourge. Various ongoing researches have been searching for the new drug candidate against COVID-19 infection. The research objective is based on the molecular docking study of inhibition of the main protease of COVID-19 by natural compounds found in Allium sativum and Allium cepa. Lipinski rule of five and Autodock 4.2 was used by using the Lamarckian Genetic Algorithm to perform Molecular docking to analyze the probability of docking. Further, ADME analysis was also performed by using SwissADME, which is freely available on the web. In the present study, we identified S-Allylcysteine sulfoxide (Alliin), S-Propyl cysteine, S-Allylcysteine, S-Ethylcysteine, S-Allylmercaptocysteine, S-Methylcysteine, S-propyl L-cysteine with binding energies (-5.24, -4.49, -4.99, -4.91, -4.79, -4.76, -5.0 kcal/mol) as potential inhibitor candidates for COVID-19. Out of 7 selected compounds, alliin showed the best binding efficacy with target protein 6LU7. In silico ADME analysis revealed that these compounds are expected to have a standard drug-like property as well. Our findings propose that natural compounds from garlic and onion can be used as potent inhibitors against the main protease of COVID-19, which could be helpful in combating the COVID-19 pandemic.

scholarly journals AKTIVITAS ANTI-RHEUMATOID ARTHRITIS DARI BRAZILIN DAN BRAZILEIN SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 153
Author(s):  
G. A. K. Amarawati ◽  
N. M. P. Susanti ◽  
N. P. L. Laksmiani
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Inflammatory Process ◽  
Joint Destruction ◽  
Protein Preparation ◽  
3D Structures ◽  
Docking Method ◽  
Molecular Docking Method

Rheumatoid arthritis is an autoimmune disease that occur by inflammation chronic which persist as a permanent symptom. That inflammatory process caused joint destruction. Production of pro-inflammatory sytokin such as Tumor Necrosis Factor Alpha (TNF-?) stimulate an autoimmunity. Active TNF-? plays a role in the occurrence of chronic inflammation, in which the formation of active TNF-? is regulated by TNF-? Converting Enzyme (TACE). Brazilin and brazilein are known to have anti-inflammatory activity and immunommodulator potentially as anti-rheumatoid arthritis. The purpose of this study were to determine the affinity and mechanisms of brazilin and brazilein against TACE proteins as anti-rheumatoid arthritis perfomed using molecular docking method. The study was conducted exploratively with several steps such as databases preparation of 3D structures brazilin, brazilein, TACE protein, optimization of brazilin and brazilein 3D structures, protein preparation, molecular docking method validation, and docking brazilin and brazilein in these proteins. The docking results are assessed from the binding energy and hydrogen bonds formed between brazilin and brazilein in proteins. The smaller value to the binding energy, will made the bond between brazilin and brazilein with proteins will be stronger and more stable. The results showed that brazilin and brazilein have activities as anti-rheumatoid arthritis because they are able to inhibit TACE proteins with respective bond energy values -7,24 for brazilin and – 7,59 kcal/mol for brazilein. These results show that brazilin and brazilein have the potential to inhibit inflammatory process and joint destruction in rheumatoid arthritis. Keywords : brazilin, brazilein, in silico, rheumatoid arthritis

scholarly journals De-novo Drug Design, Molecular Docking and In-Silico Molecular Prediction of AChEI Analogues through CADD Approaches as Anti-Alzheimer’s Agents

2020 ◽  
Vol 16 (1) ◽  
pp. 54-72 ◽  
Author(s):  
Surabhi Pandey ◽  
B.K. Singh
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Inhibitory Activity ◽  
In Silico ◽  
Active Sites ◽  
De Novo ◽  
Docking Studies ◽  
Target Protein ◽  
Design And Development ◽  
Reference Drug

Background: There are over 44 million persons who suffer with Alzheimer’s disease (AD) worldwide, no existence of cure and only symptomatic treatments are available for it. The aim of this study is to evaluate the anti-Alzheimer potential of designed AChEI analogues using computer simulation docking studies. AChEIs are the most potential standards for treatment of AD, because they have proven efficacy. Among all AChEIs donepezil possesses lowest adverse effects, it can treat mildmoderate- severe AD and only once-daily dosing is required. Therefore, donepezil is recognized as a significant prototype for design and development of new drug molecule. Methods: In this study the Inhibitory potential of the design compounds on acetylcholinesterase enzyme has been evaluated. Docking studies has been performed which further analyzed by in-silico pharmacokinetic evaluation through pharmacopredicta after that Interaction modes with enzyme active sites were determined. Docking studies revealed that there is a strong interaction between the active sites of AChE enzyme and analyzed compounds. Results: As a result 26 compounds have been indicates better inhibitory activity on AChE enzyme and all the screening parameters have also been satisfied by all 26 compounds. From these 26 compounds, six compounds 17, 18, 24, 30, 36 and 56 are found to be the most potent inhibitors of this series by insilico study through INVENTUS v 1.1 software, having highest bio-affinities i.e. - 8.51, - 7.67, - 8.30, - 7.59, - 8.71 and -7.62 kcal/mol respectively, while the standard or reference drug donepezil had binding affinity of - 6.32 kcal/mol. Conclusion: Computer aided drug design approach has been playing an important role in the design and development of novel anti- AD drugs. With the help of structure based drug design some novel analogues of donepezil have been designed and the molecular docking studies with structure based ADME properties prediction studies is performed for prediction of AChE inhibitory activity. The binding mode of proposed compounds with target protein i.e. AChE has been evaluated and the resulting data from docking studies explains that all of the newly designed analogues had significantly high affinity towards target protein compared to donepezil as a reference ligand.

scholarly journals Anti-Parkinson Drug Biperiden Inhibits Enzyme Acetylcholinesterase

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Adam Kostelnik ◽  
Alexander Cegan ◽  
Miroslav Pohanka
Keyword(s):  
Acetic Acid ◽  
Protein Structure ◽  
Binding Energy ◽  
Mechanism Of Action ◽  
In Silico ◽  
In Silico Prediction ◽  
Disease Treatment ◽  
Weak Inhibitor ◽  
Lead Structure ◽  
Experimental Findings

Biperiden is a drug used in Parkinson disease treatment and it serves also as an antiseizures compound in organophosphates poisoning. It acts as antagonist of muscarinic receptor activated by acetylcholine while the enzyme acetylcholinesterase (AChE) cleaves acetylcholine in synaptic junction into choline and acetic acid. This enzyme is inhibited by various compounds; however there has not been proposed evidence about interaction with biperiden molecule. We investigated this interaction using standard Ellman’s assay and experimental findings were critically completed with an in silico prediction by SwissDock docking software. Uncompetitive mechanism of action was revealed from Dixon plot and inhibition constant (Ki) was calculated to be 1.11 mmol/l. The lowest predicted binding energy was −7.84 kcal/mol corresponding to H-bond between biperiden molecule and Tyr 341 residuum in protein structure of AChE. This interaction seems to be further stabilized by π-π interaction with Tyr 72, Trp 286, and Tyr 341. In conclusion, biperiden appears as a very weak inhibitor but it can serve as a lead structure in a pharmacological research.

scholarly journals Elucidation of the interactions between SARS-CoV-2 Spike protein and wild and mutant types of IFITM proteins by in silico methods

2021 ◽  
Author(s):  
Nazli Irmak Giritlioglu ◽  
Gizem Koprululu Kucuk
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Protein Complexes ◽  
Protein Product ◽  
Binding Energies ◽  
Spike Protein ◽  
Web Based

COVID-19 is a viral disease that has been a threat to the whole world since 2019. Although effective vaccines against the disease have been developed, there are still points to be clarified about the mechanism of SARS-CoV-2, which is the causative agent of COVID-19. In this study, we determined the binding energies and the bond types of complexes formed by open (6VYB) and closed (6VXX) forms of the Spike protein of SARS-CoV-2 and wild and mutant forms of IFITM1, IFITM2, and IFITM3 proteins using the molecular docking approach. First, all missense SNPs were found in the NCBI Single Nucleotide Polymorphism database (dbSNP) for IFITM1, IFITM2, and IFITM3 and analyzed with SIFT, PROVEAN, PolyPhen-2, SNAP2, Mutation Assessor, and PANTHER cSNP web-based tools to determine their pathogenicity. When at least four of these analysis tools showed that the SNP had a pathogenic effect on the protein product, this SNP was saved for further analysis. Delta delta G (DDG) and protein stability analysis for amino acid changes were performed in the web-based tools I-Mutant, MUpro, and SAAFEC-SEQ. The structural effect of amino acid change on the protein product was made using the HOPE web-based tool. HawkDock server was used for molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis and binding energies of all complexes were calculated. BIOVIA Discovery Studio program was utilized to visualize the complexes. Hydrogen bonds, salt bridges, and non-bonded contacts between Spike and IFITM protein chains in the complexes were detected with the PDBsum web-based tool. The best binding energy among the 6VYB-IFITM wild protein complexes belong to 6VYB-IFITM1 (-46.16 kcal/mol). Likewise, among the 6VXX-IFITM wild protein complexes, the most negative binding energy belongs to 6VXX-IFITM1 (-52.42 kcal/mol). An interesting result found in the study is the presence of hydrogen bonds between the cytoplasmic domain of the IFITM1 wild protein and the S2 domain of 6VYB. Among the Spike-IFITM mutant protein complexes, the best binding energy belongs to the 6VXX-IFITM2 N63S complex (-50.77 kcal/mol) and the worst binding energy belongs to the 6VXX-IFITM3 S50T complex (4.86 kcal/mol). The study suggests that IFITM1 protein may act as a receptor for SARS-CoV-2 Spike protein. Assays must be advanced from in silico to in vitro for the determination of the receptor-ligand interactions between IFITM proteins and SARS-CoV-2.

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