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 Molecular Docking Terpinen-4-ol pada Protein IKK sebagai Antiinflamasi pada Aterosklerosis secara In Silico

2019 ◽  
pp. 44
Author(s):  
Putu Pradnya Pramita Dewi
Keyword(s):  
Molecular Docking ◽  
Endothelial Dysfunction ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Inflammatory Process ◽  
Chronic Inflammatory Disease ◽  
Docking Method ◽  
Result Show ◽  
Keywords Atherosclerosis ◽  
Zingiber Cassumunar

ABSTRACT   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 Nuclear Factor Kappa B (NF-kB) pathway involving IKK proteins. Terpinen4-ol is constituent found in the bangle (Zingiber cassumunar) rhizome. The purpose of this study were to determine the affinity and mechanisms of terpinen-4-ol against IKK protein as anti-inflammatory in atherosclerosis performed using molecular docking method. The docking result are assessed from the binding energy and hydrogen bonds formed between terpinen-4-ol and protein. The result showed that terpinen-4-ol has activity in inhibiting the inflammatory process because it is able to disturb IKK protein with bond energy values -4.89 kcal/mol. The molecular mechanism in inhibiting the activity of IKK protein through the formation of hydrogen bonds in these proteins. These result show that terpinen-4-ol has the potential to inhibiting inflammatory process and it caused the formation of atherosclerotic plaque can be obstructed.   Keywords: Atherosclerosis, Terpinen-4-ol, Molecular Docking, In Silico

scholarly journals Molecular Docking Sianidin dan Peonidin sebagai Antiinflamasi pada Aterosklerosis Secara In Silico

2018 ◽  
pp. 28
Author(s):  
Diajeng Putri Dwinda Saputra
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Endothelial Dysfunction ◽  
Atherosclerotic Plaque ◽  
In Silico ◽  
Inflammatory Process ◽  
3D Structure ◽  
Chronic Inflammatory Disease ◽  
Protein Preparation ◽  
Docking Method

Atherosclerosis is a chronic inflammatory disease that begins with endothelial dysfunction resulting in plaque growth in the inner walls of the arteries. Endothelial dysfunction causes endothelial activates NF-?B resulting in a transcription of proinflammatory gene supporting the growth of atherosclerotic plaque. The purple sweet potato anthocyanin is a compound known to have activity inhibiting the inflammatory process. The major anthocyanins contained in purple sweetpotato are cyanidine and peonidine. The cyanidine and peonidin activity test was performed as antiinflammatory at atherosclerosis based on their interaction on NF-?B protein using molecular docking method in silico. The stages of this research are preparation of protein structure database of NF-?B, protein preparation using Chimera1.10.1 application, preparation and optimization of cyanidin and peonidin 3D structure using HyperChem8 application, and validation of molecular docking and docking method of cyanidin and peonidin on NF-?B protein using application Autodock4.2. The results showed that cyanidine and peonidine had affinity and formed a hydrogen bond with the NF-?B protein. The bond energy between cyanidine and peonidine with the NF-?B protein is -7.92 kcal/mol and -7.86 kcal/mol which together form the hydrogen bond with the LEU472 amino acid on the binding site equal to the native ligand. Cyanidin and peonidine have the potential of activity as antiatherosklerosis because it has an affinity with the NF-?B protein so that it prevents the inflammatory process in the formation of atherosclerotic plaque.

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 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.

scholarly journals Medical Significance of Uterine Corpus Endometrial Carcinoma Patients Infected With SARS-CoV-2 and Pharmacological Characteristics of Plumbagin

2021 ◽  
Vol 12 ◽  
Author(s):  
Yongming Li ◽  
Songzuo Yu ◽  
Yu Li ◽  
Xiao Liang ◽  
Min Su ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Endometrial Carcinoma ◽  
In Silico ◽  
Prognostic Index ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Molecular Pathways ◽  
Uterine Corpus ◽  
Mitogen Activated Protein ◽  
Pharmacologically Active

BackgroundClinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis.MethodsThe clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB.ResultsThe bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU).ConclusionsBased on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

scholarly journals Molecular docking studies of natural compounds of naringin on enzymes involved in the urea cycle pathway in hyperammonemia

2020 ◽  
Vol 19 (5) ◽  
pp. 1037-1043
Author(s):  
Ramakrishnan Arumugam ◽  
Renuka Mani ◽  
Amalan Venkatesan ◽  
Senthilmurugan Sengamalai ◽  
Vijayakumar Natesan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
Sodium Benzoate ◽  
In Silico ◽  
Urea Cycle ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
In Silico Studies ◽  
Urea Cycle Enzymes

Purpose: To investigate the anti-hyperammonemic activity of naringin by molecular docking via in silico studies.Methods: Urea cycle proteins were docked to the natural compound naringin as well as a standard drug, sodium benzoate. Hydrogen bonds and binding energy were obtained using Catalytic Site Atlas and Cast P Finder Software Tool.Results: There were six urea cycle enzymes, including N-acetyl glutamate synthase, carbamoyl phosphate synthase I, ornithine transcarbamylase, argininosuccinate synthase, argininosuccinate lyase and arginase I. On evaluating protein interactions with naringin, which is dynamically  connected to the urea cycle pathway with hyperammonemia, naringin showed more hydrogen bonds and also produced higher binding energy when compared to the standard drug, sodium benzoate.Conclusion: The results of the molecular docking study show that naringin interacts with urea cycle enzymes with more hydrogen bonds and higher bonding energy than the standard drug, sodium benzoate. This supports the hypothesis that naringin can prevent experimental hyperammonemia. Keywords: Naringin, Sodium benzoate, Hyperammonemia, Urea cycle enzymes, In silico studies  

scholarly journals In Silico Design of E3 Ubiquitin-Protein Ligase NEDD4-1 Inhibitors: An Alternative Approach for Targeting the MAPK Pathway in Cancer Therapy

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 10
Author(s):  
Pirolli ◽  
Righino ◽  
Tropea ◽  
Gurrieri ◽  
Sangiorgi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cancer Therapy ◽  
In Silico ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
In Silico Design ◽  
Ubiquitin Protein Ligase ◽  
Alternative Approach ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

Among all the several targets in common use in the antitumor therapies, the pharmacologicinhibition of the MAPK (Mitogen Activated Protein Kinase) pathway represents an efficienttherapeutic approach [1]. [...]

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 

scholarly journals The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1082
Author(s):  
Amandeep Singh ◽  
Jeehoon Ham ◽  
Joseph William Po ◽  
Navin Niles ◽  
Tara Roberts ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Metastatic Potential ◽  
Pi3k Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Sequencing Data ◽  
Genetic Aberrations ◽  
Progression Model ◽  
Mitogen Activated Protein

Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.

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